{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:16:21Z","timestamp":1790288181180,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270246"],"award-info":[{"award-number":["82270246"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470280"],"award-info":[{"award-number":["82470280"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070240"],"award-info":[{"award-number":["82070240"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023MD734169"],"award-info":[{"award-number":["2023MD734169"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cardiac hypertrophy is a precursor to heart failure and represents a significant global cause of mortality, thereby necessitating timely and effective therapeutic interventions. Zinc finger protein 36 (Zfp36) is recognised as a critical regulator of ferroptosis; however, its role and underlying mechanisms in cardiac hypertrophy remain largely unexplored. This study aims to investigate the regulatory function of Zfp36 in ferroptosis within the context of cardiac hypertrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Single\u2010cell sequencing analysis demonstrated a reduction in Zfp36 expression associated with cardiac hypertrophy. Zfp36 was observed to mitigate ferroptosis and reduce hypertrophic phenotypes in cardiomyocytes subjected to Angiotensin II (Ang II) and in myocardial tissues induced by transverse aortic constriction. The ferroptosis inhibitor Ferrostatin\u20101 was shown to alleviate hypertrophy when co\u2010incubated with si\u2010Zfp36 and Ang II. Mechanistically, Zfp36 binds to the 3\u2032 untranslated region (3\u2032UTR) of Ythdc2 mRNA, facilitating its degradation. Ythdc2 subsequently binds to SLC7A11 mRNA, enhancing its decay, which leads to a reduction in glutathione (GSH) levels, thereby exacerbating ferroptosis and cardiac hypertrophy. Furthermore, overexpression of Ythdc2 reversed the protective effects conferred by Zfp36, while silencing of Ythdc2 counteracted the effects of Zfp36 knockdown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study elucidates the role of Zfp36 in cardiac hypertrophy, specifically detailing its modulatory mechanism via the Ythdc2\/SLC7A11\/GSH ferroptosis pathway. These insights lay the groundwork for innovative approaches to understanding the pathological mechanisms underlying cardiac hypertrophy and enhancing clinical interventions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Zfp36 was initially demonstrated to attenuate cardiac hypertrophy through the inhibition of ferroptosis in cardiomyocytes, providing a new target for therapeutic strategies targeting ferroptosis.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Zfp36 facilitated the degradation of Ythdc2 mRNA by binding to it, subsequently inhibiting Ythdc2\u2010mediated degradation of SLC7A11 mRNA, and maintaining GSH levels. This elucidates a previously unrecognized regulatory pathway in the context of cardiac hypertrophy.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.70247","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T11:46:03Z","timestamp":1741002363000},"source":"Crossref","is-referenced-by-count":9,"title":["Targeting Zfp36 to combat cardiac hypertrophy: Insights into ferroptosis pathways"],"prefix":"10.1002","volume":"15","author":[{"given":"Mingyu","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Department of Pharmacology (State Key Labratoray \u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research, Ministry of Education) College of Pharmacy Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiang","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy the First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Dong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Department of Pharmacology (State Key Labratoray \u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research, Ministry of Education) College of Pharmacy Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxu","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Department of Pharmacology (State Key Labratoray \u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research, Ministry of Education) College of Pharmacy Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Xiong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Department of Pharmacology (State Key Labratoray \u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research, Ministry of Education) College of Pharmacy Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzheng","family":"Cheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Department of Pharmacology (State Key Labratoray \u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research, Ministry of Education) College of Pharmacy Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aijing","family":"Shang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Department of Pharmacology (State Key Labratoray \u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research, Ministry of Education) College of Pharmacy Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaru","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Department of Pharmacology (State Key Labratoray \u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research, Ministry of Education) College of Pharmacy Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Department of Pharmacology (State Key Labratoray \u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research, Ministry of Education) College of Pharmacy Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Department of Pharmacology (State Key Labratoray \u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research, Ministry of Education) College of Pharmacy Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Department of Pharmacology (State Key Labratoray \u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research, Ministry of Education) College of Pharmacy Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saidi","family":"Jin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Department of Pharmacology (State Key Labratoray \u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research, Ministry of Education) College of Pharmacy Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyi","family":"Qi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Department of Pharmacology (State Key Labratoray \u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research, Ministry of Education) College of Pharmacy Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berezhnova Tatjana","family":"Alexandrovna","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Voronezh State Medical University Named After N.N. Burdenko  Voronezh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Department of Pharmacology (State Key Labratoray \u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research, Ministry of Education) College of Pharmacy Harbin Medical University  Harbin China"},{"name":"Department of Biopharmaceutical Sciences, College of Pharmacy Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0346-2863","authenticated-orcid":false,"given":"Zhimin","family":"Du","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Department of Pharmacology (State Key Labratoray \u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research, Ministry of Education) College of Pharmacy Harbin Medical University  Harbin China"},{"name":"State Key Laboratory of Quality Research in Chinese Medicines Macau University of Science and Technology  Macau China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4413-5495","authenticated-orcid":false,"given":"Chaoqian","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Department of Pharmacology (State Key Labratoray \u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research, Ministry of Education) College of Pharmacy Harbin Medical University  Harbin China"},{"name":"Department of Clinical Pharmacy the First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Joint International Research Laboratory of Cardiovascular Medicine Research Ministry of Education  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.067606"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00806-6"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-018-0007-y"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107258"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01018-7"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.059304"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-024-00783-1"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00703-5"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00735-4"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01962-6"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103158"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115765"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.1683"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2022.108198"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06964-4"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1631\/jzus.B2300077"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-64693-2"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202408811"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-022-00752-5"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27348-8"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101801"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40880-018-0288-x"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.317348"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01816-1"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-024-01350-1"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010858"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2024.10.011"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10991-7"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.066542"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-024-02481-y"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2022.155733"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-51318-5"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.11.044"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103035"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-023-00689-6"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000015608.37608.18"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00454.2022"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112411"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1122317"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-021-07220-z"}],"container-title":["Clinical and Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.70247","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T10:03:32Z","timestamp":1747735412000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ctm2.70247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,25]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/ctm2.70247"],"URL":"https:\/\/doi.org\/10.1002\/ctm2.70247","archive":["Portico"],"relation":{},"ISSN":["2001-1326","2001-1326"],"issn-type":[{"value":"2001-1326","type":"print"},{"value":"2001-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,25]]},"article-number":"e70247"}}