Hepatocyte CYR61 polarizes profibrotic macrophages to orchestrate NASH fibrosis
Open accessAbstract
Obesity is increasing worldwide and leads to a multitude of metabolic diseases, including cardiovascular disease, type 2 diabetes, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis (NASH). Cysteine-rich angiogenic inducer 61 (CYR61) is associated with the progression of NASH, but it has been described to have anti- and proinflammatory properties. We sought to examine the role of liver CYR61 in NASH progression. CYR61 liver-specific knockout mice on a NASH diet showed improved glucose tolerance, decreased liver inflammation, and reduced fibrosis. CYR61 polarized infiltrating monocytes promoting a proinflammatory/profibrotic phenotype through an IRAK4/SYK/NF-κB signaling cascade. In vitro, CYR61 activated a profibrotic program, including PDGFa/PDGFb expression in macrophages, in an IRAK4/SYK/NF-κB–dependent manner. Furthermore, targeted-antibody blockade reduced CYR61-driven signaling in macrophages in vitro and in vivo, reducing fibrotic development. This study demonstrates that CYR61 is a key driver of liver inflammation and fibrosis in NASH.
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Macrophages are critical effector cells involved in both the progression and resolution of fibrosis.
“Macrophages are critical effector cells involved in both the progression and resolution of fibrosis (7–9).”
From Matrix mechanical remodeled carrier-free nanosystem for programmable closed-loop reversal of liver fibrosis via STING alkylation (2025) · cites this paper as [9]
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Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · see citing works
Trimmomatic: a flexible trimmer for Illumina sequence data
Bolger, A. M., Lohse, M., & Usadel, B. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu170 · Cited by 65,548 · see citing works
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · see citing works
Integrated analysis of multimodal single-cell data
Hao, Y., Hao, S., Andersen-Nissen, E., Mauck, W. M., Zheng, S., Butler, A., Lee, M. J., Wilk, A. J., Darby, C., Zagar, M., et al. (2020) · doi:10.1101/2020.10.12.335331 · Cited by 15,508 · see citing works
Massively parallel digital transcriptional profiling of single cells
Zheng, G. X. Y., Terry, J. M., Belgrader, P., Ryvkin, P., Bent, Z. W., Wilson, R., Ziraldo, S. B., Wheeler, T. D., McDermott, G. P., Zhu, J., et al. (2017) · Nature Communications · doi:10.1038/ncomms14049 · Cited by 7,353 · see citing works
UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction
McInnes, L., Healy, J., & Melville, J. (2018) · arXiv · doi:10.48550/arxiv.1802.03426 · Cited by 7,101 · see citing works
Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention
Younossi, Z., Anstee, Q. M., Marietti, M., Hardy, T., Henry, L., Eslam, M., George, J., & Bugianesi, E. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.109 · Cited by 5,249 · see citing works
Chalasani, N., Younossi, Z. M., Lavine, J. E., Diehl, A. M., Brunt, E. M., Cusi, K. J., Charlton, M., & Sanyal, A. J. (2012) · Hepatology · doi:10.1002/hep.25762 · Cited by 3,805 · see citing works
The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)
Buzzetti, E., Pinzani, M., & Tsochatzis, E. A. (2016) · Metabolism · doi:10.1016/j.metabol.2015.12.012 · Cited by 3,119 · see citing works
Vilar-Gomez, E., Martinez-Perez, Y., Calzadilla-Bertot, L., Torres-Gonzalez, A., Gra-Oramas, B., Gonzalez-Fabian, L., Friedman, S. L., Diago, M., & Romero-Gomez, M. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.04.005 · Cited by 2,492 · see citing works
Mechanisms and disease consequences of nonalcoholic fatty liver disease
Loomba, R., Friedman, S. L., & Shulman, G. I. (2021) · Cell · doi:10.1016/j.cell.2021.04.015 · Cited by 2,002 · see citing works
Self-citationSelective depletion of macrophages reveals distinct, opposing roles during liver injury and repair
Duffield, J. S., Forbes, S. J., Constandinou, C. M., Clay, S., Partolina, M., Vuthoori, S., Wu, S., Lang, R., & Iredale, J. P. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200522675 · Cited by 1,649 · see citing works
PROMO: detection of known transcription regulatory elements using species-tailored searches
Messeguer, X., Escudero, R., Farré, D., Núñez, Ó., Martı́nez, J., & Albà, M. M. (2002) · Bioinformatics · doi:10.1093/bioinformatics/18.2.333 · Cited by 1,371 · see citing works
Daynes, R. A., Araneo, B. A., Ershler, W. B., Maloney, C., Li, G. Z., & Ryu, S. Y. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.150.12.5219 · Cited by 1,264 · see citing works
YAP1 increases organ size and expands undifferentiated progenitor cells
Camargo, F. D., Gokhale, S., Johnnidis, J. B., Fu, D., Bell, G. W., Jaenisch, R., & Brummelkamp, T. R. (2007) · Current Biology · doi:10.1016/j.cub.2007.10.039 · Cited by 1,252 · see citing works
Taylor, R. S., Taylor, R. J., Bayliss, S., Hagström, H., Nasr, P., Schattenberg, J. M., Ishigami, M., Toyoda, H., Wai-Sun Wong, V., Peleg, N., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.01.043 · Cited by 1,069 · see citing works
Macrophage heterogeneity in liver injury and fibrosis
Tacke, F., & Zimmermann, H. W. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2013.12.025 · Cited by 1,061 · see citing works
Identification of patterns in biological sequences at the ALGGEN server: PROMO and MALGEN
Farré, D. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg605 · Cited by 1,041 · see citing works
Ratziu, V., Harrison, S. A., Francque, S., Bedossa, P., Lehert, P., Serfaty, L., Romero-Gomez, M., Boursier, J., Abdelmalek, M., Caldwell, S., et al. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.01.038 · Cited by 1,035 · see citing works
Ramachandran, P., Pellicoro, A., Vernon, M. A., Boulter, L., Aucott, R. L., Ali, A., Hartland, S. N., Snowdon, V. K., Cappon, A., Gordon-Walker, T. T., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1119964109 · Cited by 1,001 · see citing works
Jun, J.-I., & Lau, L. F. (2010) · Nature Cell Biology · doi:10.1038/ncb2070 · Cited by 998 · see citing works
Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches
Guilliams, M., Bonnardel, J., Haest, B., Vanderborght, B., Wagner, C., Remmerie, A., Bujko, A., Martens, L., Thoné, T., Browaeys, R., et al. (2022) · Cell · doi:10.1016/j.cell.2021.12.018 · Cited by 985 · see citing works
Vilar-Gomez, E., Calzadilla-Bertot, L., Wai-Sun Wong, V., Castellanos, M., Aller-de la Fuente, R., Metwally, M., Eslam, M., Gonzalez-Fabian, L., Alvarez-Quiñones Sanz, M., Conde-Martin, A. F., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.04.034 · Cited by 806 · see citing works
Karlmark, K. R., Weiskirchen, R., Zimmermann, H. W., Gassler, N., Ginhoux, F., Weber, C., Merad, M., Luedde, T., Trautwein, C., & Tacke, F. (2009) · Hepatology · doi:10.1002/hep.22950 · Cited by 782 · see citing works
NAFLD as a Continuum: From Obesity to Metabolic Syndrome and Diabetes
Godoy-Matos, A. F., Silva Júnior, W. S., & Valerio, C. M. (2020) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-020-00570-y · Cited by 643 · see citing works
Remmerie, A., Martens, L., Thoné, T., Castoldi, A., Seurinck, R., Pavie, B., Roels, J., Vanneste, B., De Prijck, S., Vanhockerhout, M., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.08.004 · Cited by 592 · see citing works
Obesity Epidemiology Worldwide
Arroyo, C., & Mincey, K. D. (2016) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2016.07.012 · Cited by 588 · see citing works
Tsuchida, T., Lee, Y. A., Fujiwara, N., Ybanez, M., Allen, B., Martins, S., Fiel, M. I., Goossens, N., Chou, H.-I., Hoshida, Y., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.03.011 · Cited by 583 · see citing works
Functions 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
Tamoutounour, S., Henri, S., Lelouard, H., de Bovis, B., de Haar, C. G., van der Woude, C. J., Woltman, A. M., Reyal, Y., Bonnet, D. A., Sichien, D., et al. (2012) · European Journal of Immunology · doi:10.1002/eji.201242847 · Cited by 526 · see citing works
Seidman, J. S., Troutman, T. D., Sakai, M., Gola, A., Spann, N. J., Bennett, H., Bruni, C. M., Ouyang, Z., Li, R. Z., Sun, X., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.04.001 · Cited by 443 · see citing works
Protocol for Primary Mouse Hepatocyte Isolation
Charni‐Natan, M., & Goldstein, I. (2020) · STAR Protocols · doi:10.1016/j.xpro.2020.100086 · Cited by 431 · see citing works
Gomes, A. L., Teijeiro, A., Burén, S., Tummala, K. S., Yilmaz, M., Waisman, A., Theurillat, J.-P., Perna, C., & Djouder, N. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.05.020 · Cited by 401 · see citing works
Data exploration, quality control and testing in single-cell qPCR-based gene expression experiments
McDavid, A., Finak, G., Chattopadyay, P. K., Dominguez, M., Lamoreaux, L., Ma, S. S., Roederer, M., & Gottardo, R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts714 · Cited by 395 · see citing works
Gawrieh, S., Noureddin, M., Loo, N., Mohseni, R., Awasty, V., Cusi, K., Kowdley, K. V., Lai, M., Schiff, E., Parmar, D., et al. (2021) · Hepatology · doi:10.1002/hep.31843 · Cited by 379 · see citing works
High-dimensional analysis of the murine myeloid cell system
Becher, B., Schlitzer, A., Chen, J.-M., Mair, F., Sumatoh, H., Teng, K., Low, D., Ruedl, C., Riccardi-Castagnoli, P., Poidinger, M., et al. (2014) · Nature Immunology · doi:10.1038/ni.3006 · Cited by 357 · see citing works
Cytofkit: A Bioconductor Package for an Integrated Mass Cytometry Data Analysis Pipeline
Chen, H., Lau, M. C., Wong, M. T., Newell, E. W., Poidinger, M., & Chen, J. (2016) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1005112 · Cited by 343 · see citing works
VSIG4, a B7 family-related protein, is a negative regulator of T cell activation
Vogt, L., Schmitz, N., Kurrer, M. O., Bauer, M., Hinton, H. I., Behnke, S., Gatto, D., Sebbel, P., Beerli, R. R., Sonderegger, I., et al. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25673 · Cited by 273 · see citing works
The UCSC Genome Browser database: 2022 update
Lee, B. T., Barber, G. P., Benet-Pagès, A., Casper, J., Clawson, H., Diekhans, M., Fischer, C., Gonzalez, J. N., Hinrichs, A. S., Lee, C. M., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkab959 · Cited by 273 · see citing works
Macrophage MerTK Promotes Liver Fibrosis in Nonalcoholic Steatohepatitis
Cai, B., Dongiovanni, P., Corey, K. E., Wang, X., Shmarakov, I. O., Zheng, Z., Kasikara, C., Davra, V., Meroni, M., Chung, R. T., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.11.013 · Cited by 266 · see citing works
Kim, 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
Sierro, F., Evrard, M., Rizzetto, S., Melino, M., Mitchell, A. J., Flórido, M., Beattie, L., Walters, S. B., Tay, S. S., Lü, B., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.07.018 · Cited by 256 · 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
Schober, J. M., Chen, N., Grzeszkiewicz, T. M., Jovanovic, I., Emeson, E. E., Ugarova, T. P., Ye, R. D., Lau, L. F., & Lam, S. C.-T. (2002) · Blood · doi:10.1182/blood.v99.12.4457 · Cited by 242 · see citing works
PDGF signaling pathway in hepatic fibrosis pathogenesis and therapeutics
Ying, H., Chen, Q., Zhang, W., Zhang, H., Ma, Y., Zhang, S., Fang, J., & Yu, C.-H. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.7641 · Cited by 238 · see citing works
Obesity and nonalcoholic fatty liver disease: current perspectives
Sarwar, R., Pierce, N., & Koppe, S. (2018) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s146339 · Cited by 232 · see citing works
The PDGF system and its antagonists in liver fibrosis
Borkham‐Kamphorst, E., & Weiskirchen, R. (2015) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2015.10.002 · Cited by 179 · see citing works
Functional Roles of Syk in Macrophage-Mediated Inflammatory Responses
Yi, Y., Son, Y., Ryou, C., Sung, G., Kim, J., & Cho, J. Y. (2014) · Mediators of Inflammation · doi:10.1155/2014/270302 · Cited by 176 · see citing works
Isolation of Mouse Embryo Fibroblasts
Durkin, M. E., Qian, X., Popescu, N. C., & Lowy, D. R. (2013) · BIO-PROTOCOL · doi:10.21769/bioprotoc.908 · Cited by 174 · 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
Mooring, M., Fowl, B. H., Lum, S. Z. C., Liu, Y., Yao, K., Softic, S., Kirchner, R., Bernstein, A., Singhi, A. D., Jay, D. G., et al. (2020) · Hepatology · doi:10.1002/hep.30928 · Cited by 162 · see citing works
Self-citationFraile, J. M., Palliyil, S., Barelle, C. J., Porter, A. J., & Kovaleva, M. (2021) · Drug Design Development and Therapy · doi:10.2147/dddt.s315724 · Cited by 152 · see citing works
Reid, D. T., Reyes, J. L., McDonald, B., Vo, T., Reimer, R. A., & Eksteen, B. (2016) · PLoS ONE · doi:10.1371/journal.pone.0159524 · Cited by 145 · see citing works
Chemokine-directed immune cell infiltration in acute and chronic liver disease
Karlmark, K. R., Wasmuth, H. E., Trautwein, C., & Tacke, F. (2008) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/17474124.2.2.233 · Cited by 132 · 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
The 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
Role of Overweight and Obesity in Gastrointestinal Disease
Emerenziani, S., Guarino, M. P. L., Asensio, L. T., Altomare, A., Ribolsi, M., Balestrieri, P., & Cicala, M. (2019) · Nutrients · doi:10.3390/nu12010111 · Cited by 131 · see citing works
Wong, M. T., Chen, J., Narayanan, S., Lin, W., Anicete, R., Tan, H. K. K., de Lafaille, M. A. C., Poidinger, M., & Newell, E. W. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.05.022 · Cited by 123 · see citing works
The Effect of Sustained Inflammation on Hepatic Mevalonate Pathway Results in Hyperglycemia
Okin, D. A., & Medzhitov, R. M. (2016) · Cell · doi:10.1016/j.cell.2016.02.023 · Cited by 122 · see citing works
Crosstalk Between Liver Macrophages and Surrounding Cells in Nonalcoholic Steatohepatitis
Li, H., Zhou, Y., Wang, H., Zhang, M., Qiu, P., Zhang, M., Zhang, R., Zhao, Q., & Liu, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01169 · 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
Cardio-Metabolic Disorders in Non-Alcoholic Fatty Liver Disease
Hadi, H. E., Vincenzo, A. D., Vettor, R., & Rossato, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092215 · Cited by 97 · see citing works
Itoh, M., Suganami, T., Kato, H., Kanai, S., Shirakawa, I., Sakai, T., Goto, T., Asakawa, M., Hidaka, I., Sakugawa, H., et al. (2017) · JCI Insight · doi:10.1172/jci.insight.92902 · Cited by 94 · see citing works
Nonalcoholic Fatty Liver Disease, Diabetes Mellitus and Cardiovascular Disease: Newer Data
Mavrogiannaki, A. N., & Migdalis, I. N. (2013) · International Journal of Endocrinology · doi:10.1155/2013/450639 · Cited by 87 · see citing works
Emerging role of genomic analysis in clinical evaluation of lean individuals with NAFLD
Vilarinho, S., Ajmera, V., Zheng, M., & Loomba, R. (2021) · Hepatology · doi:10.1002/hep.32047 · Cited by 85 · see citing works
Goyal, O., Nohria, S., Goyal, P., Kaur, J., Sharma, S., Sood, A., & Chhina, R. S. (2020) · Scientific Reports · doi:10.1038/s41598-020-78342-x · Cited by 83 · see citing works
CCN1/CYR61-mediated meticulous patrolling by Ly6C low monocytes fuels vascular inflammation
Imhof, B. A., Jemelin, S., Ballet, R., Vesin, C., Schapira, M., Karaca, M., & Emre, Y. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1607710113 · Cited by 70 · 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
Krempen, K., Grotkopp, D., Hall, K. L., Bache, A., Gillan, A., Rippe, R. A., Brenner, D. A., & Breindl, M. (1999) · Europe PMC (PubMed Central) · Cited by 59 · see citing works
Han, J., Zhang, X., Lau, J. K. C., Fu, K., Lau, H. C.-H., Xu, W., Chu, E. S., Lan, H. Y., & Yu, J. Q. (2018) · The Journal of Pathology · doi:10.1002/path.5275 · Cited by 58 · see citing works
CCN1/CYR61 overexpression in hepatic stellate cells induces ER stress-related apoptosis
Borkham‐Kamphorst, E., Steffen, B. T., de Leur, E. V., Haas, U., Tihaa, L., Friedman, S. L., & Weiskirchen, R. (2015) · Cellular Signalling · doi:10.1016/j.cellsig.2015.10.013 · Cited by 55 · see citing works
Kim, T. W., Febbraio, M., Robinet, P., DuGar, B., Greene, D. J., Cerny, A., Latz, E., Gilmour, R., Staschke, K. A., Chisolm, G. M., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002242 · Cited by 55 · see citing works
Macrophages as key regulators of liver health and disease
Papachristoforou, E., & Ramachandran, P. (2022) · International review of cytology · doi:10.1016/bs.ircmb.2022.04.006 · Cited by 55 · 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
Molecular mechanism of crosstalk between immune and metabolic systems in metabolic syndrome
Hachiya, R., Tanaka, M., Itoh, M., & Suganami, T. (2022) · Inflammation and Regeneration · doi:10.1186/s41232-022-00198-7 · Cited by 54 · see citing works
Chen, Y., Chen, Y., Zhao, L., Chen, Y., Mei, M., Li, Q., Ailong, H., Varghese, Z., Moorhead, J. F., & Ruan, X. Z. (2011) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2011.06986.x · Cited by 49 · see citing works
Feng, M., Peng, H., Yao, R., Zhang, Z., Mao, G., Yu, H., & Qiu, Y. (2020) · Bone · doi:10.1016/j.bone.2020.115522 · Cited by 38 · see citing works
Lee, S., Elaskandrany, M., Lau, L. F., Lazzaro, D. R., Grant, M. B., & Chaqour, B. (2017) · Scientific Reports · doi:10.1038/s41598-017-01585-8 · Cited by 35 · see citing works
Petersen, K. F., Dufour, S., Li, F., Rothman, D. L., & Shulman, G. I. (2022) · JCI Insight · doi:10.1172/jci.insight.157906 · Cited by 30 · see citing works
Self-citationHasuzawa, N., Tatsushima, K., Wang, L., Kabashima, M., Tokubuchi, R., Nagayama, A., Ashida, K., Ogawa, Y., Moriyama, Y., & Nomura, M. (2021) · Scientific Reports · doi:10.1038/s41598-021-83144-w · Cited by 24 · see citing works
Zhang, L., Xie, Z., Yu, H., Du, H., Wang, X., Cai, J., Qiu, Y., Chen, R., Jiang, X., Liu, Z., et al. (2021) · Annals of Translational Medicine · doi:10.21037/atm-21-4012 · Cited by 12 · see citing works
Flagged first, then by citations
Research works printed but not linked: 6
- [45]Sierro F, Evrard M, Rizzetto S, Melino M, Mitchell AJ, Florido M, Beattie L, Walters SB, Tay SS, Lu B, Holz LE, Roediger B, Wong YC, Warren A, Ritchie W, McGuffog C, Weninger W, Le Couteur DG, Ginhoux F, Britton WJ, Heath WR, Saunders BM, McCaughan GW, Luciani F, MacDonald KPA, Ng LG, Bowen DG, Bertolino P, A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment. Immunity 47, 374– 388 e376 (2017). 28813662
- [50]Kim TW, Febbraio M, Robinet P, DuGar B, Greene D, Cerny A, Latz E, Gilmour R, Staschke K, Chisolm G, Fox PL, DiCorleto PE, Smith JD, Li X, The critical role of IRAK4-mediated NFκB activation in modified-LDL-induced atherosclerosis. Journal of Immunology (Baltimore, Md.: 1950) 186, 2871 (2011). 21278342 PMC3261755
- [66]Fraile JM, Palliyil S, Barelle C, Porter AJ, Kovaleva M, in Drug Design, Development and Therapy. (Dove Press, 2021), vol. 15, pp. 3997. 34588764 PMC8473845
- [74]Krempen K, Grotkopp D, Hall K, Bache A, Gillan A, Rippe RA, Brenner DA, Breindl M, Far upstream regulatory elements enhance position-independent and uterus-specific expression of the murine α1(I) collagen promoter in transgenic mice. Gene Expression 8, 151– 163 (1999). 10634317 PMC6157370
- [80]Hao Y, Hao S, Andersen-Nissen E, Mauck WM, Zheng S, Butler A, Lee MJ, Wilk AJ, Darby C, Zager M, Hoffman P, Stoeckius M, Papalexi E, Mimitou EP, Jain J, Srivastava A, Stuart T, Fleming LM, Yeung B, Rogers AJ, McElrath JM, Blish CA, Gottardo R, Smibert P, Satija R, Integrated analysis of multimodal single-cell data. Cell 184, 3573– 3587.e3529 (2021). 34062119 PMC8238499
- [85]Krempen K, Grotkopp D, Hall K, Bache A, Gillan A, Rippe RA, Brenner DA, Breindl M, Far upstream regulatory elements enhance position-independent and uterus-specific expression of the murine α1(I) collagen promoter in transgenic mice. Gene Expression 8, 151– 163 (1999). 10634317 PMC6157370
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- Authors
- Mooring, M., Yeung, G. A., Luukkonen, P., Liu, S., Akbar, M. W., Zhang, G. J., Balogun, O., Yu, X., Mo, R., Nejak-Bowen, K., Poyurovsky, M. V., Booth, C. J., Konnikova, L., Shulman, G. I., & Yimlamai, D.
- Affiliations
- University of Pittsburgh (US)
- Yale University (US)
- Kadmon Corporation (United States) (US)
- Department of Cellular and Molecular Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
- Corresponding author
- Mooring, Meghan
- Yeung, Grace A.
- Yimlamai, Dean
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2023-09-27
- Volume
- 15
- Issue
- 715
- Pages
- eade3157-eade3157
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC10874639
- OpenAlex
- W4387091740
- Cited by
- 33
- References
- 82
- Citations by year
- 2026: 12 · 2025: 16 · 2024: 5
- FWCI
- 6.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- AstraZeneca
- Yale University
- Gilead Sciences
- University of Pittsburgh
- Maze Therapeutics
- National Institutes of Health (DK120531, DK034989, CA016359, DK045735, UL1TR001863)
- Center for Research Computing, University of Pittsburgh
- National Cancer Institute (P30CA016359)
- National Institute of Diabetes and Digestive and Kidney Diseases (R03DK124743, R01DK119968, P30DK120531, P30DK034989, R01DK129552, P30DK045735)
- National Institute of Biomedical Imaging and Bioengineering (T32EB001026)
- Janssen Research and Development
- National Center for Advancing Translational Sciences
- Yale Liver Center (P30 DK-034989, DK034989)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- CYR61, nonalcoholic steatohepatitis, liver fibrosis, macrophage polarization, monocyte differentiation, liver inflammation, obesity, liver-specific knockout mice
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Disease Models, Animal, Fibrosis, Liver, Macrophages, Mice, Inbred C57BL, NF-kappa B, Mice, Knockout, Hepatocytes, Mice, Interleukin-1 Receptor-Associated Kinases, Non-alcoholic Fatty Liver Disease
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