{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T16:39:30Z","timestamp":1787330370276,"version":"build-2736575974"},"reference-count":43,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Kidney Blood Press Res"],"abstract":"<jats:p>Introduction: Ureteral scar formation is a fibrotic process linked with collagen synthesis. Although autophagy prevents collagen synthesis, its role in ureteral scarring remains unclear. Therefore, this study investigated the modulation of SESN2-mediated autophagy by verapamil during ureteral scar formation. Methods: An in vitro fibrosis model was constructed using transforming growth factor-\u03b21 (TGF-\u03b21)-stimulated primary fibroblasts. We established a rat model of ureteral stricture (US), and KN-93 was used to inhibit the phosphorylation of Ca2+\/calmodulin-dependent protein kinase II (CaMK II). Histopathological alterations and collagen accumulation in rat ureteral tissues were examined using hematoxylin-eosin and Masson staining. The levels of vimentin, \u03b1-SMA, and LC3 were determined using immunofluorescence. Autophagic flux was assessed using an mCherry-GFP-LC3 assay. mRNA and protein levels were assessed by quantitative real-time PCR and Western blot, respectively. Additionally, co-immunoprecipitation and GST pull-down assays were used to detect the binding relationship between CaMK II and lysine-specific histone demethylase 1A (KDM1A). The interaction of H3K4me2 and KDM1A with the SESN2 promoter in fibroblasts was verified using chromatin immunoprecipitation. Results: Verapamil increased autophagy in TGF-\u03b21-stimulated fibroblasts and alleviated ureteral fibrosis in US rats by inhibiting CaMK II phosphorylation (p-CaMK II) to reduce collagen synthesis. Moreover, p-CaMK II promoted the nuclear translocation of KDM1A by phosphorylating KDM1A. Additionally, the effects of KDM1A knockdown on the autophagy and collagen synthesis in TGF-induced fibroblasts were reversed by SESN2 knockdown. Finally, KDM1A knockdown further enhanced the effect of verapamil in promoting SESN2-mediated fibroblast autophagy and suppressed collagen synthesis. Conclusion: Verapamil reduced collagen synthesis during ureteral scar formation by inhibiting the phosphorylation of KDM1A by p-CaMK II, thus, decreasing the demethylation of H3K4me2 on the SESN2 promoter to enhance SESN2-mediated autophagy.<\/jats:p>","DOI":"10.1159\/000553434","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:00:49Z","timestamp":1784304049000},"page":"749-765","source":"Crossref","is-referenced-by-count":0,"title":["Verapamil Reduces Collagen Synthesis to Alleviate Ureteral Scar Formation by Inhibiting KDM1A-Mediated Epigenetic Silencing of 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