Sox9 and rbpj differentially regulate endothelial to mesenchymal transition and wound scarring in murine endovascular progenitors
Open accessAbstract
Endothelial to mesenchymal transition (EndMT) is a leading cause of fibrosis and disease, however its mechanism has yet to be elucidated. The endothelium possesses a profound regenerative capacity to adapt and reorganize that is attributed to a population of vessel-resident endovascular progenitors (EVP) governing an endothelial hierarchy. Here, using fate analysis, we show that two transcription factors SOX9 and RBPJ specifically affect the murine EVP numbers and regulate lineage specification. Conditional knock-out of Sox9 from the vasculature ( Sox9 fl/fl /Cdh5-Cre ER RosaYFP ) depletes EVP while enhancing Rbpj expression and canonical Notch signalling. Additionally, skin wound analysis from Sox9 conditional knock-out mice demonstrates a significant reduction in pathological EndMT resulting in reduced scar area. The converse is observed with Rbpj conditionally knocked-out from the murine vasculature ( Rbpj fl/fl /Cdh5-CreER RosaYFP ) or inhibition of Notch signaling in human endothelial colony forming cells, resulting in enhanced Sox9 and EndMT related gene ( Snail, Slug, Twist1, Twist2, TGF-β ) expression. Similarly, increased endothelial hedgehog signaling ( Ptch1 fl/fl /Cdh5-CreER RosaYFP ), that upregulates the expression of Sox9 in cells undergoing pathological EndMT, also results in excess fibrosis. Endothelial cells transitioning to a mesenchymal fate express increased Sox9 , reduced Rbpj and enhanced EndMT. Importantly, using topical administration of siRNA against Sox9 on skin wounds can substantially reduce scar area by blocking pathological EndMT. Overall, here we report distinct fates of EVPs according to the relative expression of Rbpj or Notch signalling and Sox9 , highlighting their potential plasticity and opening exciting avenues for more effective therapies in fibrotic diseases.
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SOX9 expression in endothelial cells induces skin wound healing.
“Recently, SOX9 expression in endothelial cells was also found to induce skin wound healing (16).”
From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [16]
The Results section, “Loss of Sox9 in the endothelium significantly impairs EndMT and reduces scarring during wound healing” (page not provided), reports the opposite direction: mice lacking endothelial Sox9 healed skin wounds significantly faster than controls. The paper also reports enhanced healing after Sox9 inhibition with siRNA. (LLM, conf=0.89)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredIn mouse, SOX9 is essential in skin wound healing.
“Previous work in mouse has shown that SOX9 is essential for the EndMT process that produces functioning heart valves, as well as in skin wound healing, and acts as a master TF (11,16,17,66).”
From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [16]
The Results section, “Loss of Sox9 in the endothelium significantly impairs EndMT and reduces scarring during wound healing” (page unavailable), reports that mice with endothelial Sox9 deletion healed skin wounds significantly faster than controls. Topical Sox9 inhibition likewise accelerated closure. The paper therefore does not support the claim that SOX9 is essential for skin wound healing in mice. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredIn mouse, SOX9 is essential for the EndMT process that produces functioning heart valves.
“Previous work in mouse has shown that SOX9 is essential for the EndMT process that produces functioning heart valves, as well as in skin wound healing, and acts as a master TF (11,16,17,66).”
From SOX9 reprograms endothelial cells by altering the chromatin landscape (2022) · cites this paper as [16]
The Discussion reports that deleting Sox9 in mouse endothelium substantially reduced EndMT and scarring, supporting a role for SOX9 in murine EndMT and wound healing. It does not establish that SOX9 is essential for the EndMT that produces functioning heart valves; its discussion of cardiac cushion EndMT concerns Slug rather than a SOX9 valve experiment (page unavailable in our copy). (LLM, conf=0.85)
Experimental — accuracy not yet measured
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Cites
Molecular mechanisms of epithelial–mesenchymal transition
Lamouille, S., Xu, J., & Derynck, R. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3758 · Cited by 8,091 · see citing works
Stöckl, S., Göttl, C., Grifka, J. K., & Grässel, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350089 · Cited by 4,670 · see citing works
Endothelial-to-mesenchymal transition contributes to cardiac fibrosis
Zeisberg, E. M., Tarnavski, O., Zeisberg, M., Dorfman, A. L., McMullen, J. R., Gustafsson, E., Chandraker, A. K., Yuan, X., Pu, W. T., Roberts, A. B., et al. (2007) · Nature Medicine · doi:10.1038/nm1613 · Cited by 2,224 · see citing works
Akiyama, H., Chaboissier, M.-C., Martin, J. F., Schedl, A., & de Crombrugghe, B. (2002) · Genes & Development · doi:10.1101/gad.1017802 · Cited by 1,721 · see citing works
Single-Cell Transcriptome Atlas of Murine Endothelial Cells
Kalucka, J. M., de Rooij, L. P. M. H., Goveia, J., Rohlenová, K., Dumas, S. J., Meta, E., Conchinha, N. V., Taverna, F., Teuwen, L.-A. M. N., Veys, K., et al. (2020) · Cell · doi:10.1016/j.cell.2020.01.015 · Cited by 1,322 · see citing works
Timmerman, L., Grego‐Bessa, J., Raya, Á., Bertrán, E., Pérez-Pomares, J. M., Díez, J., Aranda, S., Palomo‐Ponce, S., McCormick, F., Izpisúa‐Belmonte, J. C., et al. (2003) · Genes & Development · doi:10.1101/gad.276304 · Cited by 972 · see citing works
Slug and Sox9 Cooperatively Determine the Mammary Stem Cell State
Guo, W., Keckesova, Z., Donaher, J. L., Shibue, T., Tischler, V., Reinhardt, F., Itzkovitz, S., Noske, A., Zürrer‐Härdi, U., Bell, G. W., et al. (2012) · Cell · doi:10.1016/j.cell.2012.02.008 · Cited by 969 · see citing works
Therapeutic miRNA and siRNA: Moving from Bench to Clinic as Next Generation Medicine
Chakraborty, C., Sharma, A. R., Sharma, G., Doss, C. G. P., & Lee, S. (2017) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2017.06.005 · Cited by 731 · see citing works
Endothelial Cell HeterogeneityPreprint
Aird, W. C. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006429 · Cited by 729 · see citing works
Identification and isolation of a dermal lineage with intrinsic fibrogenic potential
Rinkevich, Y., Walmsley, G. G., Hu, M. S.-M., Maan, Z. N., Newman, A. M., Drukker, M., Januszyk, M., Krampitz, G. W., Gurtner, G. C., Lorenz, H. P., et al. (2015) · Science · doi:10.1126/science.aaa2151 · Cited by 695 · 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
Endothelial to Mesenchymal Transition in Cardiovascular Disease
Kovacic, J. C., Dimmeler, S., Harvey, R. P., Finkel, T., Aikawa, E. R., Krenning, G., & Baker, A. H. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.09.089 · Cited by 634 · see citing works
Evrard, S., Lecce, L., Michelis, K. C., Nomura-Kitabayashi, A., Pandey, G. S., Purushothaman, K., d’Escamard, V., Li, J. R., Hadri, L., Fujitani, K., et al. (2016) · Nature Communications · doi:10.1038/ncomms11853 · Cited by 621 · see citing works
Ingram, D. A., Mead, L. E., Moore, D. B., Woodard, W., Fenoglio, A., & Yöder, M. C. (2004) · Blood · doi:10.1182/blood-2004-08-3057 · Cited by 582 · see citing works
Hair follicle stem cells are specified and function in early skin morphogenesis
Nowak, J. A., Polak, L., Pasolli, H. A., & Fuchs, E. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.05.009 · Cited by 554 · see citing works
Leong, K. G., Niessen, K. S., Kulić, I., Raouf, A., Eaves, C. J., Pollet, I. L., & Karsan, A. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20071082 · Cited by 466 · see citing works
TGF-β signaling mediates endothelial to mesenchymal transition (EndMT) during vein graft remodeling
Cooley, B., Nevado, J., Mellad, J., Yang, D., Hilaire, C. S., Negro, A., Fang, F., Chen, G.-B., Hong, S., Walts, A., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3006927 · Cited by 414 · see citing works
Slug is a direct Notch target required for initiation of cardiac cushion cellularization
Niessen, K., Fu, Y., Chang, L., Hoodless, P. A., McFadden, D., & Karsan, A. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200710067 · Cited by 363 · see citing works
Kokudo, T., Suzuki, Y., Yoshimatsu, Y., Yamazaki, T., Watabe, T., & Miyazono, K. (2008) · Journal of Cell Science · doi:10.1242/jcs.028282 · Cited by 322 · see citing works
Noseda, M., McLean, G. W., Niessen, K. S., Chang, L., Pollet, I. L., Montpetit, R., Shahidi, R., Dorovini‐Zis, K., Li, L., Beckstead, B. L., et al. (2004) · Circulation Research · doi:10.1161/01.res.0000124300.76171.c9 · Cited by 294 · see citing works
Reassessing endothelial-to-mesenchymal transition in cardiovascular diseases
Li, Y., Lui, K. O., & Zhou, B. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0023-y · Cited by 283 · see citing works
In situ gelling systems based on Pluronic F127/Pluronic F68 formulations for ocular drug delivery
Khateb, K. A., Ozhmukhametova, E. K., Mussin, M. N., Seilkhanov, S. K., Rakhypbekov, T. K., Lau, W. M., & Khutoryanskiy, V. V. (2016) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2016.02.027 · Cited by 282 · see citing works
Moonen, J.-R. A. J., Lee, E. S., Schmidt, M., Maleszewska, M., Koerts, J. A., Brouwer, L. A., van Kooten, T. G., van Luyn, M. J. A., Zeebregts, C. J., Krenning, G., et al. (2015) · Cardiovascular Research · doi:10.1093/cvr/cvv175 · Cited by 245 · see citing works
Kumar, S., Liu, J., Pang, P. D., Krautzberger, A. M., Reginensi, A., Akiyama, H., Schedl, A., Humphreys, B. D., & McMahon, A. P. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.034 · Cited by 232 · see citing works
Self-organized vascular networks from human pluripotent stem cells in a synthetic matrix
Kusuma, S., Shen, Y., Hanjaya‐Putra, D., Mali, P., Cheng, L., & Gerecht, S. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1306562110 · Cited by 226 · see citing works
CD157 Marks Tissue-Resident Endothelial Stem Cells with Homeostatic and Regenerative Properties
Wakabayashi, T., Naito, H., Suehiro, J., Lin, Y., Kawaji, H., Iba, T., Kouno, T., Ishikawa-Kato, S., Furuno, M., Takara, K., et al. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.01.010 · Cited by 200 · see citing works
Epithelial stem cells and implications for wound repair
Plikus, M. V., Gay, D. L., Treffeisen, E. R., Wang, A., Supapannachart, R. J., & Cotsarelis, G. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.10.001 · Cited by 199 · see citing works
Naito, H., Kidoya, H., Sakimoto, S., Wakabayashi, T., & Takakura, N. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.465 · Cited by 173 · see citing works
Challenges and Opportunities in Drug Delivery for Wound Healing
Whittam, A. J., Maan, Z. N., Duscher, D., Wong, V., Barrera, J. A., Januszyk, M., & Gurtner, G. C. (2014) · Advances in Wound Care · doi:10.1089/wound.2014.0600 · Cited by 163 · see citing works
NOTCH regulation of the endothelial cell phenotype
Mack, J. J., & Iruela‐Arispe, M. L. (2018) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000425 · Cited by 160 · see citing works
SOX E genes: SOX9 and SOX8 in mammalian testis development
Barrionuevo, F. J., & Scherer, G. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.07.015 · Cited by 155 · see citing works
Identification of blood vascular endothelial stem cells by the expression of protein C receptor
Yu, Q. C., Song, W., Wang, D., & Zeng, Y. A. (2016) · Cell Research · doi:10.1038/cr.2016.85 · Cited by 146 · see citing works
Topical pluronic F-127 gel application enhances cutaneous wound healing in rats.
Kant, V., Gopal, A., Kumar, D., Gopalkrishnan, A., Pathak, N., Kurade, N., Tandan, S., & Kumar, D. (2014) · Acta Histochemica · doi:10.1016/j.acthis.2013.04.010 · Cited by 134 · see citing works
Understanding the role of SOX9 in acquired diseases: lessons from development
Pritchett, J. P., Athwal, V. S., Roberts, N. A., Hanley, N. A., & Hanley, K. P. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.12.001 · Cited by 134 · see citing works
Luanpitpong, S., Li, J., Manke, A., Brundage, K. M., Ellis, E., McLaughlin, S. L., Angsutararux, P., Chanthra, N., Voronkova, M. A., Chen, Y., et al. (2015) · Oncogene · doi:10.1038/onc.2015.351 · Cited by 118 · see citing works
Ectopic SOX9 Mediates Extracellular Matrix Deposition Characteristic of Organ Fibrosis
Hanley, K. P., Oakley, F., Sugden, S. A., Wilson, D. I., Mann, D. A., & Hanley, N. A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m707390200 · Cited by 117 · see citing works
Tomo-Seq identifies SOX9 as a key regulator of cardiac fibrosis during ischemic injury
Lacraz, G. P. A., Junker, J. P., Gladka, M. M., Molenaar, B., Scholman, K. T., Vigil-Garcia, M., Versteeg, D., de Ruiter, H., Vermunt, M. W., Creyghton, M. P., et al. (2017) · Circulation · doi:10.1161/circulationaha.117.027832 · Cited by 111 · see citing works
Lukowski, S. W., Patel, J., Andersen, S. B., Sim, S.-L., Wong, H. Y., Tay, J., Winkler, I. G., Powell, J. E., & Khosrotehrani, K. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.102 · Cited by 105 · see citing works
Self-citationIdentification of SOX9 Interaction Sites in the Genome of Chondrocytes
Oh, C., Maity, S. N., Lu, J.-F., Zhang, J., Liang, S., Coustry, F., Crombrugghe, B. D., & Yasuda, H. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010113 · Cited by 99 · see citing works
Yung, L., Sánchez‐Duffhues, G., ten Dijke, P., & Yu, P. B. (2015) · Cardiovascular Research · doi:10.1093/cvr/cvv221 · Cited by 88 · see citing works
Tumor-targeted in vivo gene silencing via systemic delivery of cRGD-conjugated siRNA
Liu, X., Wang, W., Samarsky, D. A., Liu, L., Xu, Q., Zhang, W., Zhu, G., Wu, P., Zuo, X., Deng, H., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku831 · Cited by 81 · see citing works
Notch gain of function inhibits chondrocyte differentiation via Rbpj-dependent suppression of Sox9
Chen, S., Tao, J., Bae, Y., Jiang, M., Bertin, T., Chen, Y., Yang, T., & Lee, B. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1770 · Cited by 80 · see citing works
Mouse lung contains endothelial progenitors with high capacity to form blood and lymphatic vessels
Schniedermann, J., Rennecke, M., Buttler, K., Richter, G., Städtler, A.-M., Norgall, S., Badar, M., Barleon, B., May, T., Wilting, J., et al. (2010) · BMC Cell Biology · doi:10.1186/1471-2121-11-50 · Cited by 72 · see citing works
Okada, Y., Yano, K., Jin, E., Funahashi, N., Kitayama, M., Doi, T., Spokes, K., Beeler, D. L., Shih, S., Okada, H., et al. (2007) · Circulation Research · doi:10.1161/01.res.0000269779.10644.dc · Cited by 71 · see citing works
Overman, J. P., Fontaine, F. R., Wylie‐Sears, J., Moustaqil, M. D., Huang, L. J., Meurer, M., Chiang, I. K., Lesieur, E., Patel, J., Zuegg, J., et al. (2019) · eLife · doi:10.7554/elife.43026 · Cited by 66 · see citing works
Self-citationDonovan, P., Patel, J., Dight, J., Wong, H. Y., Sim, S.-L., Murigneux, V., François, M., & Khosrotehrani, K. (2018) · Nature Communications · doi:10.1038/s41467-018-07961-w · Cited by 59 · see citing works
Self-citationKnockdown of SOX9 Inhibits the Proliferation, Invasion, and EMT in Thyroid Cancer Cells
Huang, J., & Guo, L. (2017) · Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics · doi:10.3727/096504016x14732772150307 · Cited by 58 · see citing works
Notch Signaling in Cardiac Development and Disease
de la Pompa, J. L. (2009) · Pediatric Cardiology · doi:10.1007/s00246-008-9368-z · Cited by 46 · see citing works
Patel, J., Baz, B., Wong, H. Y., Lee, J. S., & Khosrotehrani, K. (2017) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2017.12.004 · Cited by 44 · see citing works
Self-citationPatel, J., Wong, H. Y., Wang, W., Alexis, J., Shafiee, A., Stevenson, A. J., Gabrielli, B. G., Fisk, N. M., & Khosrotehrani, K. (2016) · Stem Cells · doi:10.1002/stem.2262 · Cited by 43 · see citing works
Self-citationCrosby, C. O., Valliappan, D., Shu, D., Kumar, S., Tu, C., Deng, W., Parekh, S. H., & Zoldan, J. (2019) · Tissue Engineering Part A · doi:10.1089/ten.tea.2018.0274 · Cited by 40 · see citing works
Shafiee, A., Patel, J., Hutmacher, D. W., Fisk, N. M., & Khosrotehrani, K. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.01.011 · Cited by 37 · see citing works
Self-citationScott, S. S., Braunstein, M. J., Lange, C. S., Roman, C. A. J., Smith, E. L., Joseph, D. F., & Batuman, O. (2010) · Blood · doi:10.1182/blood.v116.21.2984.2984 · Cited by 1 · see citing works
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Research works printed but not linked: 1
- [54]Koh, C. M. in Methods in Enzymology Vol. 533 (ed. Lorsch, J.) Ch. 16 (Academic Press, 2013).
Cited by
Sorted by citations
Fibroblast and myofibroblast activation in normal tissue repair and fibrosis
Younesi, F. S., Miller, A. E., Barker, T. H., Rossi, F. M. V., & Hinz, B. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00716-0 · Cited by 711 · see citing works
Pathological angiogenesis: mechanisms and therapeutic strategies
Dudley, A. C., & Griffioen, A. W. (2023) · Angiogenesis · doi:10.1007/s10456-023-09876-7 · Cited by 529 · see citing works
The Role of Myofibroblasts in Physiological and Pathological Tissue Repair
Schuster, R., Younesi, F., Ezzo, M., & Hinz, B. (2023) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041231 · Cited by 232 · see citing works
An NIR photothermal-responsive hybrid hydrogel for enhanced wound healing
Jin, L., Guo, X., Gao, D., Liu, Y., Ni, J., Zhang, Z., Huang, Y., Xu, G., Yang, Z., Zhang, X., et al. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.03.006 · Cited by 149 · see citing works
Epithelial-mesenchymal transition
Zhang, C. X., Huang, R. Y., Sheng, G., & Thiery, J. P. (2025) · Cell · doi:10.1016/j.cell.2025.08.033 · Cited by 100 · see citing works
Statins improve endothelial function via suppression of epigenetic-driven EndMT
Liu, C., Shen, M., Tan, W. L. W., Chen, I. Y., Liu, Y., Yu, X., Yang, H., Zhang, A., Liu, Y., Zhao, M., et al. (2023) · Nature Cardiovascular Research · doi:10.1038/s44161-023-00267-1 · Cited by 88 · see citing works
Macrophages in Skin Wounds: Functions and Therapeutic Potential
Sim, S.-L., Kumari, S., Kaur, S., & Khosrotehrani, K. (2022) · Biomolecules · doi:10.3390/biom12111659 · Cited by 92 · see citing works
Self-citationQi, Y., Ren, S., Ye, J., Tian, Y., Wang, G., Zhang, S., Du, L., Li, Y., Che, Y., & Ning, G. (2022) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.02.034 · Cited by 75 · see citing works
Research progress of endothelial‐mesenchymal transition in diabetic kidney disease
Chen, Y., Zou, H., Lü, H., Xiang, H., & Chen, S. (2022) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17356 · Cited by 67 · see citing works
Trogisch, F. A., Abouissa, A., Keleş, M., Birke, A., Fuhrmann, M., Dittrich, G. M., Weinzierl, N., Wink, E., Cordero, J., Elsherbiny, A., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.abq4581 · Cited by 62 · see citing works
Liu, P., Xiong, Y., Chen, L., Lin, C., Yang, Y., Lin, Z., Yu, Y., Mi, B., Liu, G., Xiao, X., et al. (2021) · Chemical Engineering Journal · doi:10.1016/j.cej.2021.132413 · Cited by 57 · see citing works
Langerhans cells are essential components of the angiogenic niche during murine skin repair
Wasko, R. R., Bridges, K., Pannone, R., Sidhu, I., Xing, Y., Naik, S., Miller‐Jensen, K., & Horsley, V. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.11.012 · Cited by 51 · see citing works
Endothelial Heterogeneity in Development and Wound Healing
Gurevich, D., David, D. T., Sundararaman, A., & Patel, J. (2021) · Cells · doi:10.3390/cells10092338 · Cited by 40 · see citing works
Self-citationResident vascular endothelial progenitor definition and function: the age of reckoning
Dight, J., Zhao, J., Styke, C., Khosrotehrani, K., & Patel, J. (2021) · Angiogenesis · doi:10.1007/s10456-021-09817-2 · Cited by 39 · see citing works
Self-citationCellular phenotypic transitions in diabetic nephropathy: An update
Cao, Y., Lin, J., Hammes, H., & Zhang, C. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1038073 · Cited by 37 · see citing works
SOX9 reprograms endothelial cells by altering the chromatin landscape
Fuglerud, B. M., Drissler, S., Lotto, J., Stephan, T. L., Thakur, A., Cullum, R., & Hoodless, P. A. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac652 · Cited by 35 · see citing works
“Previous work in mouse has shown that SOX9 is essential for the EndMT process that produces functioning heart valves, as well as in skin wound healing, and acts as a master TF (11,16,17,66).”
BackgroundYou, N., Liu, G., Yu, M., Chen, W., Fei, X., Sun, T., Han, M., Qin, Z., Wei, Z., & Wang, D. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2024.12.049 · Cited by 30 · see citing works
Yuan, H., You, Y., He, Y., Wei, Y., Zhang, Y., Min, H., Li, C. R., & Chen, J. (2023) · Environmental Science & Technology · doi:10.1021/acs.est.3c03980 · Cited by 28 · see citing works
Zhang, R., Tan, Y., Yong, C., Jiao, Y., Tang, X., & Wang, D. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.108805 · Cited by 28 · see citing works
Kim, J., Silvaroli, J. A., Vasquez-Martinez, G., Bisunke, B., Ramirez, A. V. L., Jayne, L. A., Feng, M. J. H. H., Girotra, B., Martinez, S. M. A., Vermillion, C. R., et al. (2023) · Kidney International · doi:10.1016/j.kint.2023.02.026 · Cited by 28 · see citing works
Guo, X., Xiu, F., Bera, H., Abbasi, Y. F., Chen, Y., Si, L., Liu, P., Zhao, C., Tang, X., Yu, F., et al. (2023) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2023.121085 · Cited by 28 · see citing works
Liu, M., Zhou, X., Wang, Y., Zhao, W., Zhao, X., Li, L., Xue, F., Zhang, Q., Yan, J., Su, Y., et al. (2024) · Advanced Materials · doi:10.1002/adma.202406153 · Cited by 25 · see citing works
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Lei, M., & Chen, G. (2025) · Acta Biomaterialia · doi:10.1016/j.actbio.2025.05.011 · Cited by 12 · see citing works
Jiang, H., Zhou, Y., Zhang, W., Li, H., Ma, W., Ji, X., & Zhou, C. (2025) · Cell & Bioscience · doi:10.1186/s13578-025-01393-y · Cited by 12 · see citing works
Endothelial dysfunction aggravates arterial media calcification in warfarin administered rats
den Bergh, G. V., den Branden, A. V., Opdebeeck, B., Fransen, P., Neven, E., Meyer, G. R. Y. D., D’Haese, P. C., & Verhulst, A. (2022) · The FASEB Journal · doi:10.1096/fj.202101919r · Cited by 12 · see citing works
Recombinant human collagen microneedle patches loaded with PRP for diabetic wound treatment
Wang, X., Zhang, X., Zhao, Y., Zhan, X., Hu, C., Li, H., Fan, X., Liang, J., Chen, Y., & Fan, Y. (2025) · Journal of Materials Chemistry B · doi:10.1039/d5tb00836k · Cited by 9 · see citing works
Thiery, J. P., Sheng, G., Shu, X., & Runyan, R. B. (2024) · Development · doi:10.1242/dev.200128 · Cited by 9 · see citing works
Plasma-derived exosomes contributes to endothelial-to-mesenchymal transition in Moyamoya disease
Liu, J., Chen, C., Qin, X., Wang, J., Zhang, B., & Jin, F. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e26748 · Cited by 9 · see citing works
Ling, R., Yin, X., Ma, L., Zhang, Y., Ma, Y., Gao, R., Geng, Y., Mu, X., Chen, X., Li, F., et al. (2025) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2025.139377 · Cited by 7 · see citing works
Silver‐Based Nanozyme Hydrogel with Enhanced Multienzyme Activity for Infected Wound Treatment
Wang, W., Wei, X., Gui, H., Yan, T., Xu, B., Wu, K., Liu, H., & Wang, X. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202404535 · Cited by 7 · see citing works
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Jiménez, S. A., & Piera-Velázquez, S. (2023) · Current Rheumatology Reviews · doi:10.2174/0115733971261932231025045400 · Cited by 7 · see citing works
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Savagner, P., Brabletz, T., Cheng, C., Gilles, C., Hong, T., Polette, M., Sheng, G., Stemmler, M. P., & Thompson, E. W. (2024) · Cells Tissues Organs · doi:10.1159/000536096 · Cited by 7 · see citing works
Tang, L., Zhang, J., Shao, Y., Wei, Y., Li, Y., Tian, K., Xiang, Y., Feng, C., & Zhang, Q. C. (2025) · Cell Systems · doi:10.1016/j.cels.2025.101266 · Cited by 6 · see citing works
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Vance, M. L., Nagy, D., Brunner, E., Morkotinis, V., Black, J. L., Refai, L. H., Csiszár, A., & Conley, S. M. (2025) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/j.jpet.2025.103747 · Cited by 5 · see citing works
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Zhao, J., Sormani, L., Jacquelin, S., Li, H., Styke, C., Zhou, C., Beesley, J., Oon, L., Kaur, S., Sim, S.-L., et al. (2024) · Angiogenesis · doi:10.1007/s10456-024-09927-7 · Cited by 5 · see citing works
Self-citationThe Ets2 super-enhancer modulates endothelial-mesenchymal transition during cardiac ageing
Guo, Z., Li, L., Luo, J., Xue, W., Bian, S., Zhu, Y., Huo, D., Yang, W., Ma, J., Hao, Y., et al. (2025) · Cardiovascular Research · doi:10.1093/cvr/cvaf242 · Cited by 5 · see citing works
Nano, R., Sim, S.-L., Shafiee, A., Khosrotehrani, K., & Patel, J. (2022) · STAR Protocols · doi:10.1016/j.xpro.2022.101354 · Cited by 5 · see citing works
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Balk, B., & Goodrich, D. W. (2024) · Cancer Heterogeneity and Plasticity · doi:10.47248/chp2401020010 · Cited by 4 · see citing works
He, J., Li, L., Xiong, D., Liu, F., An, J., Bai, W., Hu, Y., Liu, L., & Liu, D. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.115496 · Cited by 4 · see citing works
Wang, Y., Zhou, X., Liu, M., Huang, M., Chen, P., Li, X.-Y., Xue, F., Zhao, W., Liu, D., Li, L., et al. (2025) · Advancement of science · doi:10.1002/advs.202510545 · Cited by 5 · see citing works
Wang, S., Fu, L., Wang, B., Cai, Y., Jiang, J., & Shi, Y. (2024) · BMC Genomics · doi:10.1186/s12864-024-11175-4 · Cited by 4 · see citing works
Wang, Q., Xu, J., Xu, Y., Chen, X., Gao, X., Li, J., Xu, Q., Liu, F., & Li, Y. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202503699 · Cited by 3 · see citing works
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Jia, Y., Wang, P., Jin, X., Luo, L., Lai, K., & Li, J. (2024) · Seminars in Ophthalmology · doi:10.1080/08820538.2023.2300806 · Cited by 3 · see citing works
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Sim, S.-L., Blumenthal, A., Kaur, S., & Khosrotehrani, K. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.957833 · Cited by 3 · see citing works
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Akalın, S. A., Öcal, E., & Devecí, E. (2023) · Acta Cirúrgica Brasileira · doi:10.1590/acb388023 · Cited by 2 · see citing works
Identification and functional analysis of a new cold induced LncRNA44154
Zhang, D., Ma, S., Wang, L., & Liu, D. (2024) · Gene · doi:10.1016/j.gene.2024.148921 · Cited by 1 · see citing works
Mendoza, F. A., Piera-Velázquez, S., & Jiménez, S. A. (2026) · Journal of Molecular Medicine · doi:10.1007/s00109-026-02679-5 · Cited by 1 · see citing works
Investigation of the Sox-9 and Cited-1 Immune Activity in Placentas of Women with Placenta Accreta
Akalın, S. A., Öcal, E., & Devecí, E. (2023) · Medical Records · doi:10.37990/medr.1239182 · Cited by 1 · see citing works
Rnf20 shapes the endothelial control of heart morphogenesis and functionPreprint
Kessler, L., Gao, R., Tetik-Elsherbiny, N., Lityagina, O., Zhailauova, A., Ren, Y., Trogisch, F. A., Cordero, J., Dou, Y., Wang, Y., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.16.508288 · Cited by 1 · see citing works
Investigation of the Sox-9 and Caspase-6 Immune Activity in Placentas of Pregnant Women with GDM
Öcal, E., Akalın, S. A., & Devecí, E. (2023) · Medical Records · doi:10.37990/medr.1252256
Khosrotehrani, K., Hashemi, G., Li, H., Tan, S. X., Zhou, C., Dight, J., Li, K., Nguyen, Q. H., Roy, E., & Sormani, L. (2024) · Research Square · doi:10.21203/rs.3.rs-5457583/v1
Self-citationXi, X.-L., Yang, Y.-D., Liu, H., Jiang, J., & Wu, B. (2025) · World Journal of Hepatology · doi:10.4254/wjh.v17.i6.107329
Cao, Y., Zhang, J., Kai, X., Xue, Y., Wang, X., Wang, X., Zhang, C., Hua, Z., Wei, Y., & Yin, R. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1701701
Autoantibody reactome analysis reveals novel biomarkers for idiopathic retroperitoneal fibrosis
He, X., Ouyang, L., Meng, X., Wu, Y., Wu, T., He, Z., Yang, J., Zhu, X., Xuan, H., Song, R., et al. (2026) · Lara D. Veeken · doi:10.1093/rheumatology/keag210
Endothelial Cell Phenotypic Plasticity in Atherosclerosis
Alonso-Herranz, L., & Albarrán-Juárez, J. (2026) · Handbook of experimental pharmacology · doi:10.1007/164_2026_814
Guinamard, R., Kerevel, C., Darengosse, A., Platel, V., Sallé, L., & Simard, C. (2026) · Cell Calcium · doi:10.1016/j.ceca.2026.103163
Functional definition of endothelial progenitors by PROCR and PDGFRA co-expression
Styke, C., Kaur, S., Sim, S.-L., Zhao, J., Zhou, C., Wong, H. Y., Patel, J., Roy, E., Yoder, M. C., Harvey, R. P., et al. (2026) · Angiogenesis · doi:10.1007/s10456-026-10078-0
Self-citationTang, Q., Slarve, I., Chen, J., Zeng, N., Gu, Y., He, L., Hu, S., Alhousari, D., Xu, Z., Hua, B., et al. (2026) · Oncogene · doi:10.1038/s41388-026-03960-0
Yang, T., Liu, Z., Ran, H., Zhang, C., Wu, Q., & Xu, J. (2026) · Journal of Cardiothoracic Surgery · doi:10.1186/s13019-026-04287-3
Cutaneous endothelial cells and their roles in wound healing
Li, H., Sormani, L., Sim, S.-L., Shafiee, A., & Khosrotehrani, K. (2026) · JID Innovations · doi:10.1016/j.xjidi.2026.100539
Self-citation
- Authors
- Zhao, J., Patel, J., Kaur, S., Sim, S.-L., Wong, H. Y., Styke, C., Hogan, I., Kahler, S., Hamilton, H., Wadlow, R., Dight, J., Hashemi, G., Sormani, L., Roy, E., Yoder, M. C., Francois, M., & Khosrotehrani, K.
- Affiliations
- The University of Queensland (AU)
- Queensland University of Technology (AU)
- Corresponding author
- Khosrotehrani, Kiarash
- ORCID
- Venue
- Nature Communications
- Published
- 2021-05-07
- Volume
- 12
- Issue
- 1
- Pages
- 2564-2564
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC8105340
- OpenAlex
- W3158408472
- Cited by
- 63
- References
- 54
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 13 · 2023: 9 · 2022: 13 · 2021: 3
- FWCI
- 2.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- QUT ePrints (Queensland University of Technology) (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- IUScholarWorks (Indiana University) (submittedVersion, cc-by)
- Funders
- Department of Education and Training | Australian Research Council (DP190103187, DE180100984)
- Department of Health | National Health and Medical Research Council (APP1125290)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- endothelial-to-mesenchymal transition, SOX9, RBPJ, Notch signaling, wound scarring, fibrosis, Hedgehog signaling, PTCH1, snails, Slug, TWIST1, TWIST2, TGF-beta, siRNA therapeutics, skin wound healing
- MeSH terms
- Animals, Cell Differentiation, Endothelium, Female, Humans, Male, Mice, Inbred C57BL, Wound Healing, Signal Transduction, Transforming Growth Factor beta, Mice, Knockout, Cell Lineage, RNA, Small Interfering, Endothelial Cells, Mice, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Receptors, Notch, Hedgehog Proteins, SOX9 Transcription Factor, Gene Knockout Techniques
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