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Initiation of TGF-\u03b2 signaling requires not only its synthesis but also the conversion of latent TGF-\u03b2 to its bioactive form. However, the mechanisms governing TGF-\u03b2 activation in the kidney and their contribution to kidney fibrosis remain poorly understood. Glycoprotein A repetitions predominant (GARP) anchors latent TGF-\u03b2 on the cell surface and facilitates its bioactive release. Here, we show that GARP-mediated TGF-\u03b2 activation promotes kidney fibrosis. GARP was upregulated in both human and mouse CKD kidneys, predominantly in fibroblasts, and was induced by TNF in an NF-\u03baB\u2013dependent fashion. In multiple mouse models of kidney fibrosis, either global or fibroblast-specific deletion of GARP markedly reduced fibrosis. Mechanistically, GARP enables sustained production of active TGF-\u03b2, thereby amplifying fibroblast stimulation. Deletion of GARP in kidney fibroblasts lowered active TGF-\u03b2 levels and attenuated fibroblast activation, whereas GARP overexpression enhanced TGF-\u03b2 signaling. Notably, tamoxifen-induced deletion of GARP after fibrosis onset attenuated kidney fibrosis. Together, our findings identify GARP-mediated release of active TGF-\u03b2 as a critical step in sustaining fibroblast activation during kidney fibrosis and highlight GARP as a promising therapeutic target for CKD.<\/jats:p>","DOI":"10.1172\/jci.insight.203039","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:00:18Z","timestamp":1789660818000},"source":"Crossref","is-referenced-by-count":0,"title":["Kidney fibrosis is mediated by GARP-restricted TGF-\u03b2 activation in fibroblasts"],"prefix":"10.1172","volume":"11","author":[{"given":"Yintong","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Multi-organ Injury Prevention and Treatment; National Clinical Research Center for Kidney and Urological Diseases, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, Guangdong, 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