{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:44:48Z","timestamp":1792061088267,"version":"4.4.0"},"reference-count":58,"publisher":"Portland Press Ltd.","issue":"11","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82570869"],"award-info":[{"award-number":["82570869"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,11,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Resident renal fibroblasts are a predominant source for myofibroblasts that produce ECM to contribute to renal fibrosis in the course of chronic kidney disease (CKD). The mechanism whereby fibroblast\u2013myofibroblast transition (FMyT) is driven remains incompletely understood. In the present study, we investigated the involvement of ten\u2013eleven translocation 3 (TET3) in regulating FMyT and renal fibrosis focusing on the regulatory mechanism and translational potential. We report that TET3 deletion in primary renal fibroblasts dampened myofibroblast transition in response to pro-fibrogenic stimuli. Consistently, conditional deletion of TET3 in quiescent fibroblasts (driven by the Col1a2-Cre) or in myofibroblasts (driven by the Postn-Cre) equally attenuated renal fibrosis in mice. Integrated transcriptomic analysis combining RNA-seq and CUT&amp;Tag-seq uncovered signal peptide CUB-EGF-like domain-containing protein 3 (Scube3) as a novel downstream target for TET3. Co-culture assay confirmed that Scube3 mediated intercellular crosstalk and promoted fibroblast activation in an autocrine\/paracrine manner. Importantly, myofibroblast-specific Scube3 depletion significantly ameliorated renal fibrosis in mice. Finally, a small-molecule TET3 degrader Bobcat339 suppressed FMyT in vitro and mitigated renal fibrosis in vivo. Our data support a role for TET3 in renal fibrosis and provide proof-of-concept that targeting the TET3\u2013Scube3 axis may yield novel therapeutic solutions for treating CKD.<\/jats:p>","DOI":"10.1042\/cs20260881","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:55:51Z","timestamp":1791190551000},"page":"2411-2427","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ten\u2013eleven translocation 3 activates the TGF-\u03b2-like ligand Scube3 to promote renal fibrosis: mechanism and translational potential"],"prefix":"10.1042","volume":"140","author":[{"given":"Yajun","family":"Luo","sequence":"first","affiliation":[{"name":"1State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoqi","family":"Kang","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"2Department of Geriatric Nephrology, Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China"},{"name":"3Department of Nephrology, Affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2804-2611","authenticated-orcid":false,"given":"Yong","family":"Xu","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[{"name":"2Department of Geriatric Nephrology, Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China"},{"name":"3Department of Nephrology, Affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Wu","sequence":"additional","affiliation":[{"name":"4School of Sports and Health, Nanjing Sport Institute, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"2026101505514540600_B1","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/s41581-024-00820-6","article-title":"Chronic kidney disease and the global public health agenda: an international consensus","volume":"20","author":"Francis","year":"2024","journal-title":"Nat. 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