{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:47:14Z","timestamp":1773010034483,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The objective of this work was to investigate the role of ZFP36 in mitral valve prolapse (MVP). Mitral valve and plasma were collected to assess the expression of ZFP36, transforming growth factor \u03b2 (TGF\u2010\u03b2), collagen and elastin and apoptosis rates. Mitral valve interstitial cells (MICs) were transfected with ZFP36 plasmids to observe changes in the secretion of collagen, elastin and matrix metalloproteinases (MMPs) and apoptosis rates. MICs were exposed to TGF\u2010\u03b21 to evaluate the changes in expression of collagen, elastin, MMPs and ZFP36 and apoptosis. Subsequently, after transfection with ZFP36 plasmid, exogenous TGF\u2010\u03b21 was added to the MICs, and the secretion of collagen, elastin and MMPs and apoptosis rate were re\u2010evaluated. Finally, transcriptome and RNA immunoprecipitation (RIP) sequencing was conducted to identify downstream genes of TGF\u2010\u03b21 that could bind to ZFP36. Patients with MVP showed elevated levels of TGF\u2010\u03b21 in plasma and increased rates of apoptosis, along with higher expression of ZFP36, TGF\u2010\u03b21, collagen and elastin in the prolapsed valve. Overexpression of ZFP36 in MICs did not significantly alter the secretion of collagen or elastin or apoptosis rates. TGF\u2010\u03b21 promoted apoptosis of MICs, increased the secretion of collagen, elastin, MMP\u20103,9, ZFP36 and reduced the expression of MMP\u20101,2,13. Moreover, overexpression of ZFP36 inhibited the effects of TGF\u2010\u03b21 on MICs. Co\u2010analysis of transcriptome and RIP sequencing identified three genes: CFAP184, GTP binding protein 6 (GBP6) and HERC6. Knockdown of GBP6 reduced the pro\u2010apoptotic effects of TGF\u2010\u03b21 on MICs. ZFP36 exerts a protective role in MVP by inhibiting the effects of TGF\u2010\u03b21 on MICs. Notably, ZFP36 can mitigate the pro\u2010apoptotic effects of TGF\u2010\u03b21 on MICs through the GBP6 pathway.<\/jats:p>","DOI":"10.1113\/ep092930","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T05:03:16Z","timestamp":1762837396000},"page":"700-713","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ZFP36 inhibits the pro\u2010apoptotic effects of transforming growth factor \u03b21 on mitral valve interstitial cells via the GTP\u2010binding protein 6 pathway in mitral valve prolapse"],"prefix":"10.1113","volume":"111","author":[{"given":"Meng","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery First Affiliated Hospital with Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoyi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery First Affiliated Hospital with Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yawei","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery First Affiliated Hospital with Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology First Affiliated Hospital with Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qihan","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery First Affiliated Hospital with Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery First Affiliated Hospital with Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingyang","family":"Shi","sequence":"additional","affiliation":[{"name":"Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihu","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery First Affiliated Hospital with Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingxin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery First Affiliated Hospital with Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7941-8623","authenticated-orcid":false,"given":"Yanhu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery First Affiliated Hospital with Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-45665-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3984"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01020-13"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/08916934.2022.2103800"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.04.031"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2009.01136.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.050214"},{"issue":"5","key":"e_1_2_9_10_1","first-page":"417","article-title":"Durability of mitral valve repair for mitral regurgitation due to degenerative mitral valve disease","volume":"4","author":"David T. 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