The Matricellular Protein CCN1 Is Essential for Cardiac Development
Open accessAbstract
The matricellular protein CCN1 (formerly named CYR61) regulates cell adhesion, migration, proliferation, survival, and differentiation through binding to integrin receptors and heparan sulfate proteoglycans. Here we show that Ccn1 -null mice are impaired in cardiac valvuloseptal morphogenesis, resulting in severe atrioventricular septal defects (AVSD). Remarkably, haploinsufficiency for Ccn1 also results in delayed formation of the ventricular septum in the embryo and persistent ostium primum atrial septal defects (ASD) in ≈20% of adults. Mechanistically, Ccn1 is not required for epithelial-to-mesenchymal transformation or cell proliferation and differentiation in the endocardial cushion tissue. However, Ccn1 deficiency leads to precocious apoptosis in the atrial junction of the cushion tissue and impaired gelatinase activities in the muscular component of the interventricular septum at embryonic day 12.5, when fusion between the endocardial cushion tissue and the atrial and ventricular septa occurs, indicating that these defects may underlie the observed AVSD. Moreover, human CCN1 maps to 1p21-p31, the chromosomal location of an AVSD susceptibility gene. Together, these results provide evidence that deficiency in matrix signaling can lead to autosomal dominant AVSD, identify Ccn1 +/− mice as a genetic model for ostium primum ASD, and implicate CCN1 as a candidate gene for AVSD in humans.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CCN1 is required for cardiovascular development in embryos.
“plays essential roles in cardiovascular development during embryogenesis”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [86]
Ccn1-null mice are defective in placental vessel bifurcation and suffer severe cardiovascular defects.
“Consistent with an important role for CCN1 in angiogenesis in vivo, Ccn1-null mice are defective in placental vessel bifurcation and suffer severe cardiovascular defects [85,86].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [86]
Approximately 30% of Ccn1-null embryos fail to form chorioallantoic fusion at E8.5 and die by E9.5, whereas the remaining embryos perish at mid-gestation from placental vascular insufficiency, loss of embryonic vascular integrity, hemorrhage, and severe AVSD.
“Approximately 30% of Ccn1-null embryos fail to form chorioallantoic fusion at E8.5 and die by E9.5, whereas the remaining embryos perish at mid-gestation from placental vascular insufficiency, loss of embryonic vascular integrity, hemorrhage, and severe cardiac atrioventricular septal defect (AVSD) [85,86].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [86]
Ccn1 expression during mouse embryogenesis is tightly associated with development of skeletal, cardiovascular, and neuronal systems, and targeted disruption of Ccn1 in mice results in embryonic lethality.
“Ccn1 expression during mouse embryogenesis is tightly associated with development of the skeletal, cardiovascular, and neuronal systems [82], and targeted disruption of Ccn1 in mice results in embryonic lethality.”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [86]
Ccn1-null embryos exhibit severe defects in atrioventricular valvuloseptal morphogenesis, resulting in a common atrioventricular valve orifice that is the hallmark of complete AVSD.
“Ccn1-null embryos also exhibit severe defects in atrioventricular valvuloseptal morphogenesis, resulting in a common atrioventricular valve orifice that is the hallmark of complete AVSD [86].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [86]
Mesenchymal cells in the endocardial cushion tissue suffer premature apoptosis, preventing them from fusing properly with the atrial and ventricular septa to undergo appropriate valvuloseptal morphogenesis.
“The mesenchymal cells in the endocardial cushion tissue suffer premature apoptosis, preventing them from fusing properly with the atrial and ventricular septa to undergo apposite valvuloseptal morphogenesis.”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [86]
Although Ccn1+/− mice are largely viable, they exhibit persistent ostium primum atrial septal defects with 20% penetrance.
“Although Ccn1+/− mice are largely viable, they exhibit persistent ostium primum atrial septal defects with 20% penetrance [86].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [86]
Cites
Vu, T. H., Shipley, J. M., Bergers, G., Berger, J. E., Helms, J. A., Hanahan, D., Shapiro, S. D., Senior, R. M., & Werb, Z. (1998) · Cell · doi:10.1016/s0092-8674(00)81169-1 · Cited by 1,737 · see citing works
DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1
Jerome, L. A., & Papaioannou, V. E. (2001) · Nature Genetics · doi:10.1038/85845 · Cited by 1,076 · see citing works
Bruneau, B. G., Nemer, G. M., Schmitt, J. P., Charron, F., Robitaille, L., Caron, S., Conner, D. A., Gessler, M., Nemer, M. J., Seidman, C. E., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00493-7 · Cited by 1,048 · see citing works
Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-β
Abreu, J. G., Ketpura, N. I., Reversade, B., & Robertis, E. M. D. (2002) · Nature Cell Biology · doi:10.1038/ncb826 · Cited by 901 · see citing works
Camenisch, T. D., Spicer, A. P., Brehm-Gibson, T., Biesterfeldt, J., Augustine, M. L., Calabro, A., Kubalak, S., Klewer, S. E., & McDonald, J. A. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10272 · Cited by 901 · see citing works
Ivković, S., Yoon, B. S., Popoff, S. N., Safadi, F. F., Libuda, D. E., Stephenson, R. C., Daluiski, A., & Lyons, K. M. (2003) · Development · doi:10.1242/dev.00505 · Cited by 705 · see citing works
Diversity of function is inherent in matricellular proteins: an appraisal of thrombospondin 1.
Bornstein, P. (1995) · The Journal of cell biology · doi:10.1083/jcb.130.3.503 · Cited by 666 · see citing works
Molecular Regulation of Atrioventricular Valvuloseptal Morphogenesis
Eisenberg, L. M., & Markwald, R. R. (1995) · Circulation Research · doi:10.1161/01.res.77.1.1 · Cited by 650 · see citing works
A genetic blueprint for cardiac development
Srivastava, D., & Olson, E. N. (2000) · Nature · doi:10.1038/35025190 · Cited by 632 · see citing works
Essential Role of p38α MAP Kinase in Placental but Not Embryonic Cardiovascular Development
Adams, R. H., Porrás, A., Alonso, G., Jones, M., Vintersten, K., Panelli, S., Valladares, A., Pérez, L., Klein, R., & Nebreda, Á. R. (2000) · Molecular Cell · doi:10.1016/s1097-2765(05)00014-6 · Cited by 516 · see citing works
Babic, A. M., Kireeva, M. L., Kolesnikova, T. V., & Lau, L. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6355 · Cited by 495 · see citing works
Self-citationCYR61 (CCN1) Is Essential for Placental Development and Vascular Integrity
Mo, F.-E., Muntean, A. G., Chen, C.-C., Stolz, D. B., Watkins, S. C., & Lau, L. F. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.24.8709-8720.2002 · Cited by 416 · see citing works
Self-citationAn essential role of Bmp4 in the atrioventricular septation of the mouse heart
Jiao, K., Kulessa, H., Tompkins, K., Zhou, Y., Batts, L., Baldwin, H. S., & Hogan, B. L. M. (2003) · Genes & Development · doi:10.1101/gad.1124803 · Cited by 366 · see citing works
Itoh, T., Ikeda, T., Gomi, H., Nakao, S., Suzuki, T., & Itohara, S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.36.22389 · Cited by 356 · see citing works
Biben, C., Weber, R., Kesteven, S. H., Stanley, E. G., McDonald, L., Elliott, D. A., Barnett, L. D., Köentgen, F., Robb, L., Feneley, M. P., et al. (2000) · Circulation Research · doi:10.1161/01.res.87.10.888 · Cited by 350 · see citing works
Bartram, U., Molin, D. G. M., Wisse, L. J., Azhar, M., Sanford, L. P., Doetschman, T., Speer, C. P., Poelmann, R. E., & Groot, A. C. G. (2001) · Circulation · doi:10.1161/01.cir.103.22.2745 · Cited by 305 · see citing works
Chen, C.-C., Chen, N., & Lau, L. F. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008087200 · Cited by 305 · see citing works
Self-citationThe Angiogenic Factor Cyr61 Activates a Genetic Program for Wound Healing in Human Skin Fibroblasts
Chen, C.-C., Mo, F.-E., & Lau, L. F. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m107666200 · Cited by 300 · see citing works
Self-citationMatrix Metalloproteinase-9/Gelatinase B Is Required for Process Outgrowth by Oligodendrocytes
Oh, L. Y. S., Larsen, P. H., Krekoski, C. A., Edwards, D. R., Donovan, F. M., Werb, Z., & Yong, V. W. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-19-08464.1999 · Cited by 267 · see citing works
Leu, S.-J., Lam, S. C.-T., & Lau, L. F. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m209288200 · Cited by 247 · see citing works
Self-citationGAL4 enhancer traps expressed in the embryo, larval brain, imaginal discs, and ovary of drosophila
Manseau, L. J., Baradaran, A., Brower, D. L., Budhu, A., Elefant, F., Phan, H., Philp, A. V., Yang, M., Glover, D. M., Kaiser, K., et al. (1997) · Developmental Dynamics · doi:10.1002/(sici)1097-0177(199707)209:3 · Cited by 241 · see citing works
Dor, Y., Camenisch, T. D., Itin, A., Fishman, G. I., McDonald, J. A., Carmeliet, P., & Keshet, E. (2001) · Development · doi:10.1242/dev.128.9.1531 · Cited by 240 · see citing works
Missense Mutations in CRELD1 Are Associated with Cardiac Atrioventricular Septal Defects
Robinson, S. W., Morris, C. D., Goldmuntz, E., Reller, M. D., Jones, M. A., Steiner, R. D., & Maslen, C. L. (2003) · The American Journal of Human Genetics · doi:10.1086/374319 · Cited by 229 · see citing works
Development of the heart: (2) Septation of the atriums and ventricles
Anderson, R. H., Webb, S., Brown, N. A., Lamers, W. H., & Moorman, A. F. M. (2003) · Heart · doi:10.1136/heart.89.8.949 · Cited by 186 · see citing works
CCN Proteins - A New Family of Cell Growth and Differentiation Regulators
Perbal, B., & Takigawa, M. (2005) · IMPERIAL COLLEGE PRESS eBooks · doi:10.1142/9781860946899 · Cited by 134 · see citing works
Chen, N., Leu, S.-J., Todorović, V., Lam, S. C.-T., & Lau, L. F. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406813200 · Cited by 132 · see citing works
Self-citationThe matrix protein CCN1 (CYR61) induces apoptosis in fibroblasts
Todorovicç, V., Chen, C.-C., Hay, N., & Lau, L. F. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200504015 · Cited by 132 · see citing works
Self-citationHilfiker-Kleiner, D., Kaminski, K., Kaminska, A., Fuchs, M., Klein, G., Podewski, E., Grote, K., Kiian, I., Wollert, K. C., Hilfiker, A., et al. (2004) · Circulation · doi:10.1161/01.cir.0000127952.90508.9d · Cited by 110 · see citing works
Young, B. B., Gordon, M. K., & Birk, D. E. (2000) · Developmental Dynamics · doi:10.1002/(sici)1097-0177(200004)217:4 · Cited by 100 · see citing works
Lopes, S. M. C. D. S., Feijen, A., Korving, J., Korchynskyi, O., Larsson, J., Karlsson, S., ten Dijke, P., Lyons, K. M., Goldschmeding, R., Doevendans, P. A., et al. (2004) · Developmental Dynamics · doi:10.1002/dvdy.20162 · Cited by 97 · see citing works
Song, W., Jackson, K., & McGuire, P. G. (2000) · Developmental Biology · doi:10.1006/dbio.2000.9919 · Cited by 91 · see citing works
Rupp, P. A., Fouad, G. T., Egelston, C. A., Reifsteck, C. A., Olson, S. B., Knosp, W. M., Glanville, R. W., Thornburg, K. L. R., Robinson, S. W., & Maslen, C. L. (2002) · Gene · doi:10.1016/s0378-1119(02)00696-0 · Cited by 90 · see citing works
Promoter function and structure of the growth factorinducible immediate early gene<i>cyr</i>61
Latinkic, B. V., Brien, T. P. O., & Lau, L. F. (1991) · Nucleic Acids Research · doi:10.1093/nar/19.12.3261 · Cited by 87 · see citing works
Self-citationSheffield, V. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.1.117 · Cited by 86 · see citing works
<i>Xenopus Cyr61</i>regulates gastrulation movements and modulates Wnt signalling
Latinkic, B. V., Mercurio, S., Bennett, B., Hirst, E. M. A., Xu, Q., Lau, L. F., Mohun, T. J., & Smith, J. C. (2003) · Development · doi:10.1242/dev.00449 · Cited by 77 · see citing works
Self-citationTargeted Mutagenesis of the Angiogenic Protein CCN1 (CYR61)
Leu, S.-J., Chen, N., Chen, C.-C., Todorović, V., Bai, T., Juric, V., Liu, Y., Yan, G., Lam, S. C.-T., & Lau, L. F. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407850200 · Cited by 72 · see citing works
Self-citationThe human growth factor-inducible immediate early gene, CYR61, maps to chromosome 1p
Jay, P., Bergé-Lefranc, J. L., Marsollier, C., Méjean, C., Taviaux, S., & Berta, P. (1997) · Oncogene · doi:10.1038/sj.onc.1200986 · Cited by 67 · see citing works
Analysis of CRELD1 as a candidate 3p25 atrioventicular septal defect locus (AVSD2)
Zatyka, M., Priestley, M., Ladusans, E. J., Fryer, A. E., Mason, J. B., Latif, F., & Maher, E. R. (2005) · Clinical Genetics · doi:10.1111/j.1399-0004.2005.00435.x · Cited by 51 · see citing works
Differential localization of Mox-1 and Mox-2 proteins indicates distinct roles during development
Candia, A. F., & Wright, C. V. E. (1996) · The International Journal of Developmental Biology · doi:10.1387/ijdb.9032023 · Cited by 47 · see citing works
Cell death and differentiation in the development of the endocardial cushion of the embryonic heart
Abdelwahid, E., Pelliniemi, L. J., & Jokinen, E. (2002) · Microscopy Research and Technique · doi:10.1002/jemt.10159 · Cited by 45 · see citing works
Perez, S. E., Cano, D. A., Dao-Pick, T., Rougier, J.-P., Werb, Z., & Hebrok, M. (2005) · Diabetes · doi:10.2337/diabetes.54.3.694 · Cited by 40 · see citing works
Cardiac Morphogenesis and Dysmorphogenesis: An Immunohistochemical Approach
Waller, B. R., & Wessels, A. (2003) · Humana Press eBooks · doi:10.1385/1-59259-685-1:151 · Cited by 29 · see citing works
Expression of tissue inhibitor of metalloproteinases (TIMPs) during early cardiac development
Brauer, P. R., & Cai, D. H. (2002) · Mechanisms of Development · doi:10.1016/s0925-4773(02)00016-3 · Cited by 28 · see citing works
Cardiac Morphogenesis and Dysmorphogenesis: I. Normal Development
Wessels, A., & Markwald, R. R. (2003) · Humana Press eBooks · doi:10.1385/1-59259-065-9:239 · Cited by 27 · see citing works
Panek, A. N., & Bäder, M. (2006) · Hypertension · doi:10.1161/01.hyp.0000208603.97395.44 · Cited by 17 · see citing works
INTEGRIN-MEDIATED CCN FUNCTIONS
Lau, L. F., & Lam, S. C. T. (2005) · CCN Proteins · doi:10.1142/9781860946899_0003 · Cited by 16 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Jun, J.-I., & Lau, L. F. (2010) · Nature Cell Biology · doi:10.1038/ncb2070 · Cited by 998 · see citing works
“CCN1 is a potent inducer of angiogenesis and Ccn1 -null mice are embryonic lethal, owing to defects in cardiovascular developmen”
BackgroundSelf-citationTaking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets
Jun, J.-I., & Lau, L. F. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3599 · Cited by 606 · see citing works
Self-citationFunctions and mechanisms of action of CCN matricellular proteins
Chen, C.-C., & Lau, L. F. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2008.07.025 · Cited by 549 · see citing works
“These findings suggest that CCN1 may be a candidate gene for human AVSD.”
BackgroundInfluentialSelf-citationMatricellular Proteins in Cardiac Adaptation and Disease
Frangogiannis, N. G. (2012) · Physiological Reviews · doi:10.1152/physrev.00008.2011 · Cited by 440 · see citing works
“Although heterozygous CCN1 / mice were viable and fertile, 20% of them had ostium primum ASDs (294).”
BackgroundInfluentialCCN1/CYR61: the very model of a modern matricellular protein
Lau, L. F. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0778-3 · Cited by 338 · see citing works
“Consistent with an important role for CCN1 in angiogenesis in vivo, Ccn1-null mice are defective in placental vessel bifurcation and suffer severe cardiovascular defects [85, 86].”
BackgroundInfluentialSelf-citationKim, K.-H., Chen, C.-C., Monzon, R. I., & Lau, L. F. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00049-13 · Cited by 261 · see citing works
“Since Ccn1 is essential for cardiovascular development, germ line Ccn1 knockout mice are embryonic lethal (33, 34).”
BackgroundSelf-citationGenetics of Congenital Heart Disease
Williams, K., Carson, J. C., & Lo, C. W. Y. (2019) · Biomolecules · doi:10.3390/biom9120879 · Cited by 198 · see citing works
Matricellular Protein CCN1 Activates a Proinflammatory Genetic Program in Murine Macrophages
Bai, T., Chen, C.-C., & Lau, L. F. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902792 · Cited by 173 · see citing works
Self-citationThe matricellular protein CCN1 mediates neutrophil efferocytosis in cutaneous wound healing
Jun, J.-I., Kim, K.-H., & Lau, L. F. (2015) · Nature Communications · doi:10.1038/ncomms8386 · Cited by 173 · see citing works
Self-citationKubota, S., & Takigawa, M. (2014) · Clinical Science · doi:10.1042/cs20140264 · Cited by 165 · see citing works
Mechanisms of tissue fusion during development
Ray, H. J., & Niswander, L. A. (2012) · Development · doi:10.1242/dev.068338 · Cited by 150 · see citing works
“Ccn1 may promote fusion through induction of matrix metallopeptidase 2 (Mmp2), which contributes to tissue remodeling, and by promoting cell survival (Mo and Lau, 2006).”
BackgroundCytotoxicity of TNFα is regulated by integrin‐mediated matrix signaling
Chen, C., Young, J. L., Monzon, R. I., Chen, N., Todorović, V., & Lau, L. F. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601596 · Cited by 143 · see citing works
“Consistently, Ccn1-null mice suffer embryonic lethality due to cardiovascular defects (Mo et al, 2002; Mo and Lau, 2006), whereas”
BackgroundSelf-citationNeonatal and Adult Cardiovascular Pathophysiological Remodeling and Repair
Norris, R. A., Borg, T. K., Butcher, J. T., Baudino, T. A., Banerjee, I., & Markwald, R. R. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1420.005 · Cited by 130 · see citing works
Norris, R. A., Moreno‐Rodriguez, R. A., Hoffman, S., & Markwald, R. R. (2009) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-009-0063-5 · Cited by 127 · see citing works
“It is interesting to note that the matricellular proteins periostin, βigH3, CCN1, and CCN2 are capable of interacting with αv, β3, and β1 integrins and are each expressed in the developing heart (Chen and Lau 2009; Chuva de Sousa Lopes et al. 2004; Mo and Lau 2006; Surveyor and Brigstock 1999).”
BackgroundConnective Tissue Growth Factor Is Required for Normal Follicle Development and Ovulation
Nagashima, T., Kim, J., Li, Q., Lydon, J. P., DeMayo, F. J., Lyons, K. M., & Matzuk, M. M. (2011) · Molecular Endocrinology · doi:10.1210/me.2011-1045 · Cited by 118 · see citing works
Grote, K., Salguero, G., Ballmaier, M., Dangers, M., Drexler, H., & Schieffer, B. (2007) · Blood · doi:10.1182/blood-2006-07-036202 · Cited by 117 · see citing works
“et al recently reported CCN1-induced MMP-2 levels in cardiomyocytes.(16) Enhanced MMP activity has been shown to be assoziated with angiogenesis.”
BackgroundGene delivery of TGF-β1 induces arthrofibrosis and chondrometaplasia of synovium in vivo
Watson, R., Gouze, E., Levings, P. P., Bush, M. L., Kay, J. D., Scott-Jorgensen, M., Dacanay, E. A., Reith, J. W., Wright, T. W., & Ghivizzani, S. C. (2010) · Laboratory Investigation · doi:10.1038/labinvest.2010.145 · Cited by 119 · see citing works
Smad7 Is Required for the Development and Function of the Heart
Chen, Q., Chen, H., Zheng, D., Kuang, C., Fang, H., Zou, B., Zhu, W., Bu, G., Jin, T., Wang, Z., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m807233200 · Cited by 114 · see citing works
CCN1 induces hepatic ductular reaction through integrin αvβ5–mediated activation of NF-κB
Kim, K.-H., Chen, C.-C., Alpini, G., & Lau, L. F. (2015) · Journal of Clinical Investigation · doi:10.1172/jci79327 · Cited by 109 · see citing works
Self-citationExtracellular Matrix Communication and Turnover in Cardiac Physiology and Pathology
Takawale, A. R., Sakamuri, S. S. V. P., & Kassiri, Z. (2015) · Comprehensive physiology · doi:10.1002/cphy.c140045 · Cited by 114 · see citing works
Role of CCN, a vertebrate specific gene family, in development
Katsube, K., Sakamoto, K., Tamamura, Y., & Yamaguchi, A. (2008) · Development Growth & Differentiation · doi:10.1111/j.1440-169x.2009.01077.x · Cited by 103 · see citing works
“…the aorta and AVSD caused by precocious apoptosis in the atrial junction of the cushion tissue and impaired gelatinase activities in the muscular component of the interventricular septum, when fusion between the endocardial cushion tissue and the atrial and ventricular septa occurs (Mo & Lau 2006).”
BackgroundGharibeh, L., Komati, H., Bossé, Y., Boodhwani, M., Heydarpour, M., Fortier, M., Hassanzadeh, R., Ngu, J. M. C., Mathieu, P., Body, S. C., et al. (2018) · Circulation · doi:10.1161/circulationaha.117.029506 · Cited by 94 · see citing works
The matricellular protein CCN1 in tissue injury repair
Kim, K., Won, J. H., Cheng, N., & Lau, L. F. (2018) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-018-0450-x · Cited by 87 · see citing works
Self-citationHeath, E., Tahri, D., Andermarcher, E., Schofield, P. N., Fleming, S., & Boulter, C. A. (2008) · BMC Developmental Biology · doi:10.1186/1471-213x-8-18 · Cited by 89 · see citing works
“A requirement for another CCN family member, CYR61, in development of the endocardial cushions has recently been reported [36].”
BackgroundLee, K.-B., Byun, H., Park, S. H., Park, C.-Y., Lee, S., & Rho, S. B. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.10.016 · Cited by 77 · see citing works
“cell adhesion, migration, embryogenesis, and wound healing [6,9–12].”
BackgroundCui, S., Li, X., Yang, F., Dai, S., Han, Z., Liu, K., Liu, B., Yuan, Q., Cui, Z., Zhang, Y., et al. (2018) · Journal of the American Heart Association · doi:10.1161/jaha.118.009111 · Cited by 72 · see citing works
Matricellular proteins of the Cyr61/CTGF/NOV (CCN) family and the nervous system
Malik, A. R., Liszewska, E., & Jaworski, J. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00237 · Cited by 71 · see citing works
“CCN1+/− mice are viable, but 20% of the adult mice have ostium primum atrial septal defects (Mo and Lau, 2006).”
BackgroundJuric, V., Chen, C.-C., & Lau, L. F. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00064-09 · Cited by 70 · see citing works
Self-citationThe CCN family acting throughout the body: recent research developments
Kubota, S., & Takigawa, M. (2013) · BioMolecular Concepts · doi:10.1515/bmc-2013-0018 · Cited by 70 · see citing works
Franzen, C. A., Chen, C.-C., Todorović, V., Juric, V., Monzon, R. I., & Lau, L. F. (2009) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-09-0017 · Cited by 66 · see citing works
Self-citationCCN1 interlinks integrin and hippo pathway to autoregulate tip cell activity
Park, M.-H., Kim, A. K., Manandhar, S., Oh, S.-Y., Jang, G.-H., Kang, L., Lee, D., Hyeon, D. Y., Lee, S.-H., Lee, H., et al. (2019) · eLife · doi:10.7554/elife.46012 · Cited by 62 · see citing works
Regulation of pancreatic function by connective tissue growth factor (CTGF, CCN2)
Charrier, A., & Brigstock, D. R. (2012) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2012.07.001 · Cited by 64 · see citing works
“An essential role during embryonic development has been shown by targeted gene deletions in mice for (i) CYR61/CCN1 which show numerous lethal angiogenic and vascular deficiencies [11, 12]; (ii) CTGF/CCN2 which exhibit widespread chondrodysplasia, defective endochondral ossification, reduced growth plate angiogenesis…”
BackgroundKrupska, I., Bruford, E. A., & Chaqour, B. (2015) · Human Genomics · doi:10.1186/s40246-015-0046-y · Cited by 60 · see citing works
“Consistent with these observations, conventional deletion of the Cyr61 gene in mice caused severe atrioventricular septal defects (AVSD) [16].”
BackgroundInfluentialCCN1 protects cardiac myocytes from oxidative stress via β1 integrin–Akt pathway
Yoshida, Y., Togi, K., Matsumae, H., Nakashima, Y., Kojima, Y., Yamamoto, H., Ono, K., Nakamura, T., Kita, T., & Tanaka, M. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.01.195 · Cited by 59 · see citing works
CCN1 interacts with integrins to regulate intestinal stem cell proliferation and differentiation
Won, J. H., Choi, J. S., & Jun, J.-I. (2022) · Nature Communications · doi:10.1038/s41467-022-30851-1 · Cited by 59 · see citing works
CCN1 is an opsonin for bacterial clearance and a direct activator of Toll-like receptor signaling
Jun, J.-I., & Lau, L. F. (2020) · Nature Communications · doi:10.1038/s41467-020-15075-5 · Cited by 54 · see citing works
Self-citationKlingenberg, R., Aghlmandi, S., Liebetrau, C., Räber, L., Gencer, B., Nanchen, D., Carballo, D., Akhmedov, A. T., Montecucco, F., Zoller, S., et al. (2017) · European Heart Journal · doi:10.1093/eurheartj/ehx640 · Cited by 55 · see citing works
“Indeed, Cyr61 knockout mice undergo embryonic lethality due to impaired vascular integrity during placental development and atrioventricular septal defects.(22,23) Cyr61 mediates endothelial proliferation, tubule formation, and neovascularization in an integrin-dependent manner(24,25) and promotes recruitment of CD34þ…”
BackgroundLi, Z., Yan, G., Diao, Q., Yu, F., Li, X., Sheng, X., Liu, Y., Dai, Y., Zhou, H., Zhen, X., et al. (2019) · Stem Cell Research & Therapy · doi:10.1186/s13287-019-1272-3 · Cited by 55 · see citing works
Chintala, H., Krupska, I., Yan, L., Lau, L. F., Grant, M. B., & Chaqour, B. (2015) · Development · doi:10.1242/dev.121913 · Cited by 52 · see citing works
Self-citationBowen, C. J., Zhou, J., Sung, D. C., & Butcher, J. T. (2015) · Developmental Biology · doi:10.1016/j.ydbio.2015.07.012 · Cited by 52 · see citing works
“We and others have previously shown that both migration and matrix condensation by AV cushion mesenchyme is adhesion dependent (Butcher et al., 2007a; Ghatak et al., 2014; Mo and Lau, 2006).”
Chen, C.-C., Kim, K.-H., & Lau, L. F. (2015) · Oncogene · doi:10.1038/onc.2015.190 · Cited by 51 · see citing works
“CCN1 is critical for placental angiogenesis and cardiac valvuloseptal morphogenesis during embryonic development (6;7).”
BackgroundSelf-citationKoentges, C., Pepin, M. E., Muesse, C., Pfeil, K., Alvarez, S. V. V., Hoppe, N., Hoffmann, M. M., Odening, K. E., Sossalla, S. T., Zirlik, A., et al. (2017) · Basic Research in Cardiology · doi:10.1007/s00395-017-0666-6 · Cited by 44 · see citing works
“Of the remaining ten genes, several are known to affect cardiac physiology: cysteine-rich angiogenic inducer 61 (CYR61), which may be essential for cardiac development [43]; four-and-a-half LIM domains 1 (FHL1), lack of which may blunt the hypertrophic response following TAC and mutations of which have been implicated…”
BackgroundChaqour, B. (2019) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-019-00529-3 · Cited by 37 · see citing works
The Roles of CCN1/CYR61 in Pulmonary Diseases
Zhu, Y., Almuntashiri, S., Han, Y., Wang, X., Somanath, P. R., & Zhang, D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21217810 · Cited by 35 · see citing works
“Heart Endocardial cells, mesenchymal cells [42]”
Zhao, X., Ding, E., Yu, O. M., Xiang, S. Y., Tan‐Sah, V. P., Yung, B. S., Hedgpeth, J., Neubig, R. R., Lau, L. F., Brown, J. H., et al. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.07.017 · Cited by 36 · see citing works
“Global CCN1 gene deletion results in embryonic lethality associated with altered cardiac development [24] and Drexler's laboratory reported that CCN1 expression is highly upregulated in the myocardium of patients with heart failure or ischemic myopathy [25].”
BackgroundSelf-citationJiang, R., Tang, J., Zhang, X., He, Y., Yu, Z., Chen, S., Xia, J., Lin, J., & Ou, Q. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.810671 · Cited by 36 · see citing works
“org 10 Previous studies on CCN1 mainly focused on tumor, tissue damage repair (39, 40), cardiovascular development (41) and so on.”
BackgroundCyr61/CCN1 and CTGF/CCN2 mediate the proangiogenic activity of VHL -mutant renal carcinoma cells
Chintalapudi, M. R., Markiewicz, M., Kose, N., Dammai, V., Champion, K. J., Hoda, R. S., Trojanowska, M. E., & Hsu, T. (2008) · Carcinogenesis · doi:10.1093/carcin/bgn019 · Cited by 36 · see citing works
“5 due to failure in chorioallantoic fusion, and ~70% die at mid-gestation with placental vascular defects, hemorrhage of embryonic vessels, and defects in heart partitions (18,19).”
BackgroundYan, L., & Chaqour, B. (2013) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-013-0206-6 · Cited by 34 · see citing works
Chaqour, B., & Karrasch, C. C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103487 · Cited by 32 · see citing works
“Loss of function of these proteins cause severe vascular defects and embryonic or perinatal lethality, setting them apart from other matricellular proteins of the vascular matrisome [74,75].”
BackgroundHoldener, B. C., Percival, C. J., Grady, R. C., Cameron, D. C., Berardinelli, S. J., Zhang, A., Neupane, S., Takeuchi, M., Jimenez-Vega, J. C., Uddin, S. M. Z., et al. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz225 · Cited by 31 · see citing works
CCN1 and CCN2: blood brothers in angiogenic action
Lau, L. F. (2012) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-012-0169-z · Cited by 28 · see citing works
“Ccn1-null mice are embryonic lethal due to severe defects in cardiac valvuloseptal morphogenesis, impaired placentation, and loss of vascular integrity (Mo et al. 2002; Mo and Lau 2006).”
BackgroundSelf-citationEmerging roles of CCN proteins in vascular development and pathology
Klenotic, P. A., Zhang, C., & Lin, Z. (2016) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-016-0332-z · Cited by 26 · see citing works
“5 (Kireeva et al. 1997; Mo and Lau 2006; Mo et al. 2002), with subsequent expression in all major arteries within the circulatory system.”
BackgroundCCN1–Yes-Associated Protein Feedback Loop Regulates Physiological and Pathological Angiogenesis
Lee, S., Ahad, A., Luu, M., Moon, S., Caesar, J., Cardoso, W. V., Grant, M. B., & Chaqour, B. (2019) · Molecular and Cellular Biology · doi:10.1128/mcb.00107-19 · Cited by 26 · see citing works
“As a transcriptional coactivator, YAP controls gene transcription on a genomewide scale, yet YAP deletion phenocopied the vascular defects associated with CCN1 deficiency in mice (16, 17).”
BackgroundVulnerability of the Developing Heart to Oxygen Deprivation as a Cause of Congenital Heart Defects
Kenchegowda, D., Liu, H., Thompson, K. N., Luo, L., Martin, S. S., & Fisher, S. A. (2014) · Journal of the American Heart Association · doi:10.1161/jaha.114.000841 · Cited by 25 · see citing works
CCN family member 1 deregulates cholesterol metabolism and aggravates atherosclerosis
Zhao, J., Chen, H., Wei, J., Leu, S. J., & Lee, T. (2018) · Acta Physiologica · doi:10.1111/apha.13209 · Cited by 25 · see citing works
“Especially, loss of function of CCN1 induces early embryonic death due to defective angiogenesis during embryogenesis.(15,16) In addition, CCN1 expression can be upregulated under certain conditions such as inflammation, tissue repair, and wound healing.”
BackgroundSu, B., & Mo, F. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2014.02.019 · Cited by 24 · see citing works
Self-citationHsu, P., Su, B.-C., Kuok, Q.-Y., & Mo, F. (2013) · Cardiovascular Research · doi:10.1093/cvr/cvt001 · Cited by 23 · see citing works
“CCN1 is dynamically expressed in developing cardiovascular and skeletal systems during embryogenesis, and embryonic Ccn1-null mice die from the cardiovascular defects caused by excessive apoptosis in developing vessels or hearts.(15,16) In adults, CCN1 expression is largely silenced in most tissue, but is redeployed u…”
BackgroundSelf-citationPaternal hypercholesterolemia elicits sex-specific exacerbation of atherosclerosis in offspring
Hernandez, R., Li, X., Shi, J., Dave, T. R., Zhou, T., Chen, Q., & Zhou, C. (2024) · JCI Insight · doi:10.1172/jci.insight.179291 · Cited by 22 · see citing works
“CCN1 and CCN2 are matricellular proteins that are essential for cardiovascular development during embryogenesis (52, 53, 87, 88).”
Why do humans need thrombospondin-1?
Kaur, S., & Roberts, D. D. (2023) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-023-00722-5 · Cited by 21 · see citing works
Structural insights into regulation of CCN protein activities and functions
Monsen, V. T., & Attramadal, H. (2023) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-023-00768-5 · Cited by 19 · see citing works
“2002; Mo and Lau 2006), CCN2 deficient mice died perinatally from respiratory failure due to thoracic skeletal abnormalities caused by impaired endochondral ossification as well as dysmorphic vasculature (Ivkovic et al.”
BackgroundThe contribution of adhesion signaling to lactogenesis
Morrison, B. L., & Cutler, M. L. (2010) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-010-0099-6 · Cited by 19 · see citing works
“…(Grzeszkiewicz et al. 2001; Lin et al. 2005), survival (Babic et al. 1999; Leu et al. 2002; Lin et al. 2003), growth (Abreu et al. 2002; Ivkovic et al. 2003), differentiation (Mori et al. 1999; Brigstock 2003) and angiogenesis (Babic et al. 1999; Mo et al. 2002; Lin et al. 2003; Mo and Lau 2006).”
BackgroundJang, G. H., Park, I. S., Yang, J. H., Bischoff, J. E., & Lee, Y. M. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.11.031 · Cited by 19 · see citing works
“CYR61 deficient mice show severe atrioventricular septal defects (AVSD) accompanying endocardial cushion defects [17].”
BackgroundHviid, C. V. B., Samulin Erdem, J., Drechsler, S., Weixelbaumer, K., Ahmed, M. S., Attramadal, H., Redl, H., Bahrami, S., Osuchowski, M. F., & Aasen, A. O. (2014) · Shock · doi:10.1097/shk.0000000000000105 · Cited by 15 · see citing works
“It occupies a central role in cardiovascular development (13), acts as a proangiogenic factor in the adult (14, 15), and has a role in vascular injury-repair mechanisms (16).”
BackgroundCCN1 Mutation is Associated with Atrial Septal Defect
Perrot, A., Schmitt, K. R. L., Roth, E.-M. G., Stiller, B., Posch, M. G., Browne, E. N. L., Timmann, C., Horstmann, R. D., Berger, F. F., & Özcelik, C. (2014) · Pediatric Cardiology · doi:10.1007/s00246-014-1001-8 · Cited by 18 · see citing works
“In these animals, Ccn1 haploinsufficiency caused precocious apoptosis in the atrial junction of the cushion tissue and impaired gelatinase activities in the muscular component of the interventricular septum, when fusion between the endocardial cushion tissue and the atrial and ventricular septa occurred [9].”
BackgroundInfluentialThe matricellular protein CCN1 regulates TNF‐α induced vascular endothelial cell apoptosis
Zhang, J. C., Wu, G., & Dai, H. (2015) · Cell Biology International · doi:10.1002/cbin.10469 · Cited by 17 · see citing works
“…member 1 (CCN1, also referred to as cysteine-rich angiogenic inducer 61), is a matricellular protein of the CCN family and has an essential role as an angiogenic factor in cardiovascular development (Babic et al., 1998; Mo et al., 2002; Mo and Lau, 2006) and neovascularization during tissue repair.”
BackgroundBae, K. B., Kim, M. O., Yu, D. H., Shin, M. J., Kim, H. J., Yuh, H. S., Ji, Y. R., Kim, J., Kim, J., Hyun, B. H., et al. (2011) · Transgenic Research · doi:10.1007/s11248-010-9476-4 · Cited by 17 · see citing works
“Previous studies have shown that abnormally enhanced apoptosis activity can lead to various cardiac defects, such as abnormal ventricular development, including ventricular septal defect, thin ventricular wall, and ventricular non-compaction (Gaussin et al. 2002; Mo and Lau 2006; Liang et al. 2007; Song et al. 2007).”
BackgroundCYR61 overexpression associated with the development and poor prognosis of ovarian carcinoma
Shen, H., Cai, M., Zhao, S., Wang, H., Li, M., Yao, S., & Jiang, N. (2014) · Medical Oncology · doi:10.1007/s12032-014-0117-2 · Cited by 15 · see citing works
Roberts, D. D., & Lau, L. F. (2010) · Springer eBooks · doi:10.1007/978-3-642-16555-9_11 · Cited by 15 · see citing works
Self-citationExtracellular Matrix Communication and Turnover in Cardiac Physiology and Pathology
Takawale, A. R., Sakamuri, S. S. V. P., & Kassiri, Z. (2015) · Comprehensive physiology · doi:10.1002/j.2040-4603.2015.tb00624.x · Cited by 14 · see citing works
Atrial expression of the CCN1 and CCN2 proteins in chronic heart failure
Bonda, T. A., Kamiński, K. A., Dziemidowicz, M., Литвинович, С. Н., Kożuch, M., Hirnle, T., Dmitruk, I., Chyczewski, L., & Winnicka, M. M. (2012) · Folia Histochemica et Cytobiologica · doi:10.5603/fhc.2012.0014 · Cited by 13 · see citing works
The regulation and functions of the matricellular CCN proteins induced by shear stress
Wang, Y.-K., Weng, H.-K., & Mo, F. (2023) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-023-00760-z · Cited by 12 · see citing works
“Gene-knockout (KO) studies demonstrate major functions of CCN proteins in both cardiovascular and skeletal systems (Hall-Glenn et al., 2012; Heath et al. 2008; Ivkovic et al. 2003; Kim et al. 2018; Mo and Lau 2006; Mo et al. 2002; Williams et al. 2021), which will be the main focus of this review.”
BackgroundSelf-citationFanter, C. E., Lin, Z., Keenan, S. W., Janzen, F. J., Mitchell, T. S., & Warren, D. E. (2019) · Journal of Experimental Biology · doi:10.1242/jeb.213918 · Cited by 11 · see citing works
Chakrabarti, M., Chattha, A., Nair, A., Jiao, K., Potts, J. D., Wang, L., Branch, S., Harrelson, S., Khan, S. R., & Azhar, M. (2023) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd10120483 · Cited by 9 · see citing works
Wren, G. H., & Davies, W. (2024) · Essays in Biochemistry · doi:10.1042/ebc20230098 · Cited by 9 · see citing works
“…defects) [44,45], (iii) deletion of the Ccn3 gene in mice results in enlargement and abnormal modeling of the endocardial cushions, septal defects, and ventricular hypertrophic cardiomyopathy [46], and (iv) deletion of Ccn1 in mice results in impaired cardiac valvuloseptal morphogenesis [47].”
Raissadati, A., Nykänen, A. I., Tuuminen, R., Syrjälä, S. O., Krebs, R., Arnaudova, R., Rouvinen, E., Wang, X., Poller, W. C., & Lemström, K. (2015) · Transplant International · doi:10.1111/tri.12639 · Cited by 9 · see citing works
A functional polymorphism in the CYR61 (IGFBP10) gene is associated with prostate cancer risk
Tao, L., Chen, J., Zhou, H., Qin, C., Li, P., Cao, Q., Li, J., Ju, X., Zhu, C., Wang, M., et al. (2012) · Prostate Cancer and Prostatic Diseases · doi:10.1038/pcan.2012.41 · Cited by 9 · see citing works
The Extracellular Matrix Protein CCN1 Dictates TNFα and FasL Cytotoxicity In Vivo
Chen, C.-C., Juric, V., & Lau, L. F. (2011) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4419-6612-4_63 · Cited by 8 · see citing works
“tions of Ccn1 and Ccn2 in mice result in embryonic and peri-natal lethality due to cardiovascular and skeletal defects, respectively [11–13], although Ccn3-null mice”
BackgroundSelf-citationGan, Y., Wei, L., Wang, Y.-Z., Kou, Z., Liang, T., Ding, G.-W., Ding, Y., & Xie, D. (2020) · Molecular Medicine Reports · doi:10.3892/mmr.2020.11761 · Cited by 8 · see citing works
Correlations Between CCN1 Immunoexpression and Myocardial Histologic Lesions in Sudden Cardiac Death
Papetta, A., Gakiopoulou, H., Agapitos, E. B., Patsouris, E., & Lazaris, A. C. (2013) · American Journal of Forensic Medicine & Pathology · doi:10.1097/paf.0b013e31828d69b5 · Cited by 8 · see citing works
“Neovascularization in mechanically stressed, smooth muscleY rich organs is particularly is promoted by various mechanoresponsive angiogenic factors including CCN1, formerly known as cysteine-rich 61 (Cyr61), a functionally multifaceted matricellular protein that appears in the extracellular environment especially duri…”
BackgroundMatricellular protein CCN1 mediates doxorubicin-induced cardiomyopathy in mice
Hsu, P.-L., & Mo, F. (2016) · OncoTarget · doi:10.18632/oncotarget.9162 · Cited by 8 · see citing works
“CCN1 is dynamically expressed in the cardiovascular system during embryogenesis and Ccn1-null mice die prenatally from cardiovascular defects [15, 16].”
BackgroundSelf-citationA sticky situation: CCN1 promotes both proliferation and apoptosis of cancer cells
Leask, A. (2009) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-009-0079-x · Cited by 7 · see citing works
“…that is essential for cardiovascular development during embryogenesis; moreover, its expression in the adult is associated with pathologies involving angiogenesis and inflammation, including play wound healing, atherosclerosis, and tumorigenesis (Babic et al. 1998; Mo et al. 2002; Mo and Lau 2006).”
BackgroundLiu, C., Liang, W., He, X., Owusu‐Agyeman, M., Wu, Z., Zhou, Y., Cao, Y., Zhang, C., Liu, J., Jiang, J., et al. (2019) · Cardiorenal Medicine · doi:10.1159/000501929 · Cited by 7 · see citing works
Bo, K. O. N. G., Liu, Y., & Lü, X. (2008) · Chinese Medical Journal · doi:10.1097/00029330-200807020-00002 · Cited by 7 · see citing works
Extracellular matrix in cardiac morphogenesis, fibrosis, and regeneration
Punde, A., Rayrikar, A., Maity, S., & Patra, C. (2025) · Cells and Development · doi:10.1016/j.cdev.2025.204023 · Cited by 7 · see citing works
Matricellular proteins: From cardiac homeostasis to immune regulation
Li, M., Chen, H., Zhang, J., Wu, Y., & Xu, Y. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117463 · Cited by 6 · see citing works
Expression of beta 2 integrin (CD18) in embryonic mouse and chicken heart
Oliveira, L. A. M., BAKER, R. K., Klewer, S. E., & Kitten, G. T. (2010) · Brazilian Journal of Medical and Biological Research · doi:10.1590/s0100-879x2010000100005 · Cited by 6 · see citing works
Morano, D., Berto, S., Lapucci, C., Baldinazzo, L. W., Prandstraller, D., & Farina, A. (2018) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-018-0321-4 · Cited by 5 · see citing works
Wessels, M. W., van de Laar, I. M. B. H., Roos‐Hesselink, J. W., Strikwerda, S., Majoor‐Krakauer, D. F., Vries, B. B. A. D., Kerstjens‐Frederikse, W. S., Vos, Y. J., de Graaf, B. M., Bertoli‐Avella, A. M., et al. (2009) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.32594 · Cited by 5 · see citing works
CCN1 : A Dermo‐Epidermal Crosstalk Mediator and Regulatory Protein in Cutaneous Homeostasis
Wu, Y., Lin, Y., Li, L., Guo, M., Wu, Y., & Yi, F. (2025) · Experimental Dermatology · doi:10.1111/exd.70157 · Cited by 4 · see citing works
Chen, Q., Liao, Z., Wang, Z., Zhang, H., & Wu, C. (2025) · Bioactive Materials · doi:10.1016/j.bioactmat.2025.09.039 · Cited by 4 · see citing works
“In addition, Ccn1 and Egr1 are key factors in the process of cardiac development for promoting proliferation and differentiation of cardiomyocytes [46,47].”
Yang, W., Bai, J., Song, X., Zhang, S., Chen, N., You, T., Kang, Y., Li, Z., Xie, D., & Xie, X. (2021) · Environmental Science and Pollution Research · doi:10.1007/s11356-021-14428-x · Cited by 4 · see citing works
“Ccn1-null mice have AVSD or VSD phenotype, and some Ccn1 haploinsufficient mice have ASD phenotype (Mo and Lau 2006).”
InfluentialDesign and Analysis of CCN Gene Activity Using CCN Knockout Mice Containing LacZ Reporters
Jiang, J., Hu, Z., & Lyons, K. M. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-6430-7_28 · Cited by 4 · see citing works
Kaur, S., & Roberts, D. D. (2021) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-020-00598-9 · Cited by 4 · see citing works
Zhao, Y., Gu, L., Chen, Y., Lin, Y., Xing, J., Xu, D., Su, Z., & Huang, Z. (2025) · Cardiovascular Therapeutics · doi:10.1155/cdr/6813183 · Cited by 3 · see citing works
“It is constitutively expressed in mouse hearts, and systemic knockout of the CCN1 gene can lead to abnormal development of mouse embryonic hearts [11, 12].”
Poloni, J. D. F., & Bonatto, D. (2015) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25156 · Cited by 2 · see citing works
Li, Y., Luo, J., Fang, B., Du, G., Tian, T., Liu, F., Li, X., & Yang, Y. (2021) · Hereditas · doi:10.1186/s41065-021-00180-2 · Cited by 2 · see citing works
“showed that the CCN1 gene deletion may impair cardiac valvuloseptal morphogenesis in mice, which leads to severe atrioventricular septal defects, because the deletion of CCN1 can lead to premature apoptosis of cells at the atrial junction of endocardial cushion tissue and to reduce gelatinase activity in the intervent…”
BackgroundNon-Syndromic atrioventricular septal defects
Patel, S. S., Romitti, P. A., SCHOLZ, T. D., Murray, J. C., Burns, T. L., & Mahoney, L. T. (2010) · doi:10.17077/etd.5l5qvwi4 · Cited by 2 · see citing works
Polymorphisms in congenital heart disease and extracardiac disorders
Islam, D. M. S., & Auliahadi, S. (2025) · Clinica Chimica Acta · doi:10.1016/j.cca.2025.120693 · Cited by 1 · see citing works
O-GlcNAcylation as a Metabolic Integrator in Cardiovascular Physiology and Disease
Malik, S. S., Pi, X., & Xie, L. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27114662 · Cited by 1 · see citing works
Construction and Analysis of an Allelic Series of Ccn1 Knockin Mice
Monzon, R. I., Kim, K., & Lau, L. F. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-6430-7_30 · Cited by 1 · see citing works
Self-citation
- Authors
- Mo, F.-E., & Lau, L. F.
- Affiliations
- University of Illinois Chicago (US)
- Venue
- Circulation Research
- Published
- 2006-10-27
- Volume
- 99
- Issue
- 9
- Pages
- 961-969
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC1626492
- OpenAlex
- W2129300074
- Cited by
- 112
- References
- 46
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 9 · 2018: 5 · 2017: 2 · 2016: 6 · 2015: 12 · 2014: 7 · 2013: 6 · 2012: 6
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA046565, CA-46565)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- CYR61, matricellular proteins, atrioventricular septal defect, primum atrial septal defect, endocardial cushion, interventricular septum, apoptosis, gelatinase activity, haploinsufficiency, congenital heart disease, integrins, heparan sulfate proteoglycans
- MeSH terms
- Animals, Endocardium, Heart, Heart Septal Defects, Heart Septal Defects, Atrial, Heart Septum, Heart Valves, Heterozygote, Mesoderm, Mice, Transgenic, Myocardium, Apoptosis, Immediate-Early Proteins, Genetic Predisposition to Disease, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Cell Proliferation, Mice, Cysteine-Rich Protein 61
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
