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Following injury, early alterations in the extracellular matrix precede the development of kidney fibrosis and represent potential therapeutic targets to improve kidney repair. In this context, studies from our laboratory and others have shown that the matricellular protein SMOC2 can be targeted to decrease inflammation and tubulointerstitial fibrosis after kidney injury. Tubular epithelial cells (TECs), which are abundant and particularly susceptible to injury, play a central role in maladaptive repair; however, whether SMOC2 affects their function after kidney injury has not been explored. In this study, we showed that SMOC2 localized to the basement membrane of injured TECs across 3 murine models of kidney injury. Our in vitro studies demonstrate that SMOC2 induced a partial epithelial-to-mesenchymal (EMT) transition in TECs. We further demonstrated that its extracellular calcium-binding domain mediated binding to the decellularized extracellular matrix and accounted for most of its effects on TECs. Mechanistically, SMOC2 promoted partial EMT through an integrin-dependent pathway. Together, these findings provide mechanistic insight into how SMOC2 drives maladaptive repair by modulating TEC behavior and identify its calcium-binding domain as a key functional mediator.<\/jats:p>","DOI":"10.1172\/jci.insight.198555","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T17:03:36Z","timestamp":1786554216000},"source":"Crossref","is-referenced-by-count":0,"title":["SMOC2 promotes partial epithelial-mesenchymal transition and maladaptive repair in renal tubular epithelial cells"],"prefix":"10.1172","volume":"11","author":[{"given":"Schrodinger","family":"Cenatus","sequence":"first","affiliation":[{"name":"Maisonneuve-Rosemont Hospital Research Centre, Montreal, Canada."},{"name":"Programmes de biologie mol\u00e9culaire, Facult\u00e9 de m\u00e9decine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Gao","sequence":"additional","affiliation":[{"name":"Maisonneuve-Rosemont Hospital Research Centre, Montreal, Canada."},{"name":"D\u00e9partement de Pharmacologie et Physiologie, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Henley","sequence":"additional","affiliation":[{"name":"Maisonneuve-Rosemont Hospital Research Centre, Montreal, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Lamarche","sequence":"additional","affiliation":[{"name":"Maisonneuve-Rosemont Hospital Research Centre, Montreal, Canada."},{"name":"D\u00e9partement de M\u00e9decine, Facult\u00e9 de M\u00e9decine, Universit\u00e9 de Montr\u00e9al, Succ. 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