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Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Bazedoxifene (BAZ), a selective estrogen receptor modulator, has recently been demonstrated to inhibit the IL-6\/STAT3 signaling pathway; however, its direct effects on cardiac fibroblasts and the underlying mechanisms remain unclear. Isoproterenol (ISO)-stimulated Sprague\u2013Dawley neonatal rat cardiac fibroblasts (CFs) were employed as an in vitro model. CCK-8 assay, flow cytometry, Transwell migration assay, ELISA, qRT-PCR, and Western blot were applied to evaluate the effects of BAZ on CF activation, proliferation, migration, and collagen synthesis. Additionally, IL-6 overexpression via lentivirus (Lv-IL-6) was used to assess mediation by IL-6\/STAT3 signaling. BAZ (5 \u03bcmol\/L) significantly inhibited ISO-induced CF proliferation by inducing G0\/G1 cell-cycle arrest; migration and upregulation of \u03b1-SMA and Collagen I\/III were reduced; IL-6, TGF-\u03b21, and hydroxyproline concentrations in the conditioned medium were decreased; STAT3 phosphorylation was significantly suppressed. Supplementation with Lv-IL-6 partially reversed these effects. The suppression of ISO-induced CF activation and fibrotic phenotype was associated with inhibition of IL-6 expression and blockade of IL-6\/STAT3 signaling, suggesting the involvement of this pathway in the anti-fibrotic effects of BAZ. These findings provide in vitro evidence supporting BAZ as a candidate anti-myocardial fibrosis agent.<\/jats:p>","DOI":"10.3390\/cimb48090879","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:33:32Z","timestamp":1788262412000},"page":"879","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bazedoxifene Attenuates Isoproterenol-Induced Cardiac Fibroblast Activation and Fibrotic Phenotype via Modulation of the IL-6\/STAT3 Signaling Axis"],"prefix":"10.3390","volume":"48","author":[{"given":"Xiangyun","family":"Chen","sequence":"first","affiliation":[{"name":"School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taomei","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyue","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixue","family":"He","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaofeng","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/s41588-023-01371-5","article-title":"Genetics of myocardial interstitial fibrosis in the human heart and association with disease","volume":"55","author":"Nauffal","year":"2023","journal-title":"Nat. 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