{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T02:42:45Z","timestamp":1789872165378,"version":"4.0.1"},"reference-count":43,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82170245"],"award-info":[{"award-number":["82170245"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82370284"],"award-info":[{"award-number":["82370284"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Research and Development Program of Hubei Province","award":["2023BCB017"],"award-info":[{"award-number":["2023BCB017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Despite the clinical efficacy of doxorubicin (DOX), effective strategies to prevent its cardiotoxicity are still lacking. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), has demonstrated cardioprotective properties; however, its role and mechanism in DOX-induced cardiotoxicity (DIC) remain unclear. In this study, Finerenone treatment was found to significantly alleviate DOX-induced cardiac dysfunction and pathological remodeling in both mouse models and cultured cells. Mechanistically, molecular docking suggests that Finerenone may directly bind to Latent Transforming Growth Factor Beta Binding Protein 2 (LTBP2), a key regulator of TGF-\u03b2 bioavailability. This potential binding could inhibit the LTBP2\u2013TGF-\u03b2 axis, thereby suppressing DOX-induced activation and subsequent Smad3 phosphorylation. The importance of this pathway was supported by the similar anti-fibrotic effects observed with the TGF-\u03b2 inhibitor LY2109761. However, our findings on the direct binding of Finerenone to LTBP2 are preliminary and require further validation through additional experimental approaches. These results identify LTBP2 as a novel direct target of Finerenone and reveal an additional mechanism underlying its cardioprotective action, suggesting its potential repurposing for the prevention of DIC.<\/jats:p>","DOI":"10.3390\/biom15121703","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T10:50:38Z","timestamp":1764931838000},"page":"1703","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting LTBP2 Reveals a Novel Anti-Cardiac Remodeling Mechanism of Finerenone Against Doxorubicin-Induced Cardiotoxicity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2785-2129","authenticated-orcid":false,"given":"Heng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saiyang","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanlan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Wang","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5507-8925","authenticated-orcid":false,"given":"Bo","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/s44161-024-00507-y","article-title":"Cytotoxic T cells drive doxorubicin-induced cardiac fibrosis and systolic dysfunction","volume":"3","author":"Bayer","year":"2024","journal-title":"Nat. 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