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Its specific role in renal fibrosis and underlying mechanisms remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The global knockout of HDAC11 mice and FT895, a selective inhibitor of HDAC11, were utilized to assess the role of HDAC11 in renal fibrosis following unilateral ureteral obstruction (UUO) injury in mice. Immunostaining was employed to analyze renal expression of HDAC11 and infiltration of macrophages. Immunoblot analysis was used to analyze the expression and\/or phosphorylation of proteins associated with partial epithelial-mesenchymal transition (pEMT) in the kidney and cultured renal proximal tubular cells (RPTCs). RT-PCR was used to analyze the expression of various proinflammatory cytokines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HDAC11 was predominantly expressed in renal epithelial cells, with its expression increasing in the kidney following UUO. This upregulation correlated with excessive collagen deposition and was associated with increased levels of fibronectin, collagen I, and \u03b1-smooth muscle actin, alongside reduced E-cadherin expression. Both global deletion of HDAC11 and treatment with the selective inhibitor FT895 significantly reduced collagen accumulation and the expression of fibronectin and collagen I, while preserving E-cadherin levels. HDAC11 inhibition also led to a decrease in histone H3 phosphorylation at serine 10, a marker of G2\/M cell cycle arrest, and reduced the expression of Snail and Twist\u2014key transcription factors involved in pEMT. Similar effects were observed in TGF \u03b21-stimulated RPTCs in vitro treated with FT895 or subjected to HDAC11 silencing via siRNA. Additionally, FT895 treatment attenuated the expression of multiple pro-inflammatory cytokines and reduced macrophage infiltration in obstructed kidneys. Both pharmacological inhibition and genetic ablation of HDAC11 suppressed activation of profibrotic signaling pathways, including Smad3, STAT3, and NF-\u03baB, in both in vitro and in vivo models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings indicate that HDAC11 is crucial for renal fibrosis development by promoting pEMT and G2\/M phase cell cycle arrest in renal epithelial cells through multiple profibrotic signaling pathways. Therefore, targeting HDAC11 may be a promising therapeutic strategy to alleviate renal fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s10020-025-01367-3","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T08:34:14Z","timestamp":1763800454000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HDAC11 promotes renal fibrosis by induing partial epithelial-mesenchymal transition and G2\/M phase arrest in renal epithelial cells"],"prefix":"10.1186","volume":"31","author":[{"given":"Yingjie","family":"Guan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengchen","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyuan","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiying","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting C.","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shougang","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,22]]},"reference":[{"key":"1367_CR1","doi-asserted-by":"publisher","first-page":"6841","DOI":"10.1158\/1078-0432.CCR-09-0547","volume":"15","author":"J Arts","year":"2009","unstructured":"Arts J, King P, Marien A, Floren W, Belien A, Janssen L, et al. 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