{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:18:30Z","timestamp":1788297510369,"version":"build-2803163510"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":41,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Postdoctoral Initiation Fund of Qingyuan People\u2019s Hospital","award":["20210401"],"award-info":[{"award-number":["20210401"]}]},{"name":"Xinjiang Uygur Autonomous Region Human Resources and Social Security Department","award":["Tianchi Talents  Introduction Program-Young Doctoral Program"],"award-info":[{"award-number":["Tianchi Talents  Introduction Program-Young Doctoral Program"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,17]]},"abstract":"<jats:p>\n                    Fibrosis is the final common pathway leading to end-stage chronic kidney disease (CKD). However, the function of protein palmitoylation in renal fibrosis and the underlying mechanisms remain unclear. In this study, we observed that expression of the palmitoyltransferase ZDHHC18 was significantly elevated in unilateral ureteral obstruction (UUO) and folic acid\u2013induced (FA-induced) renal fibrosis mouse models and was significantly upregulated in fibrotic kidneys of patients with CKD. Functionally, tubule-specific deletion of ZDHHC18 attenuated tubular epithelial cells\u2019 partial epithelial-mesenchymal transition (EMT) and then reduced the production of profibrotic cytokines and alleviated tubulointerstitial fibrosis. In contrast, ZDHHC18 overexpression exacerbated progressive renal fibrosis. Mechanistically, ZDHHC18 catalyzed the palmitoylation of HRAS, which was pivotal for its translocation to the plasma membrane and subsequent activation. HRAS palmitoylation promoted downstream phosphorylation of MEK\/ERK and further activated Ras-responsive element\u2013binding protein 1 (RREB1), enhancing SMAD binding to the\n                    <jats:italic>Snai1<\/jats:italic>\n                    <jats:italic>cis<\/jats:italic>\n                    -regulatory regions. Taken together, our findings suggest that ZDHHC18 plays a crucial role in renal fibrogenesis and represents a potential therapeutic target for combating kidney fibrosis.\n                  <\/jats:p>","DOI":"10.1172\/jci180242","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T12:46:21Z","timestamp":1738845981000},"source":"Crossref","is-referenced-by-count":30,"title":["ZDHHC18 promotes renal fibrosis development by regulating HRAS palmitoylation"],"prefix":"10.1172","volume":"135","author":[{"given":"Di","family":"Lu","sequence":"first","affiliation":[{"name":"Nephrology Department, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulibositan","family":"Aji","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University, State Key Laboratory of Pathogenesis, 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