{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:56:44Z","timestamp":1791482204619,"version":"4.3.4"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012165","name":"Key Technologies Research and Development Program","doi-asserted-by":"publisher","award":["2021YFF1000602 (J.W.)"],"award-info":[{"award-number":["2021YFF1000602 (J.W.)"]}],"id":[{"id":"10.13039\/501100012165","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017592","name":"Key Science and Technology Program of Shaanxi Province","doi-asserted-by":"publisher","award":["2023-CX-TD-57 (J.W.)"],"award-info":[{"award-number":["2023-CX-TD-57 (J.W.)"]}],"id":[{"id":"10.13039\/501100017592","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Pathological cardiac hypertrophy, a major risk factor for heart failure, is regulated by complex transcriptional networks. We previously identified the transcription factor ZBED6 as a key regulator for skeletal muscle hypertrophy, its role in the cardiac hypertrophy remains unexplored. Here, we report that ZBED6 is a key suppressor of pathological cardiac hypertrophy. ZBED6 is markedly reduced in myocardial tissues from patients with cardiac hypertrophy. ZBED6-deficient pigs exhibited cardiac hypertrophy with diastolic dysfunction. Integrative transcriptomic and ChIP-seq analyses identified MEOX1 as a direct negative target of ZBED6. Loss of ZBED6 upregulates MEOX1 transcription, which subsequently activated ERK1\/2 signaling, leading to impaired autophagy-induced hypertrophy. Knockdown of MEOX1 reduced ERK1\/2 phosphorylation and mitigated cardiomyocyte hypertrophy induced by ZBED6 deficiency. Similarly, pharmacological inhibition of ERK1\/2 restored autophagy and alleviated hypertrophy in ZBED6-depleted cardiomyocytes. Collectively, these findings define a previously unrecognized ZBED6\u2013MEOX1\u2013ERK1\/2 axis that critically regulates cardiac hypertrophy and represents a potential therapeutic target.<\/jats:p>","DOI":"10.1371\/journal.pgen.1012329","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:34:33Z","timestamp":1791480873000},"page":"e1012329","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["ZBED6 deficiency drives pathological cardiac hypertrophy through MEOX1\u2013ERK1\/2\u2013dependent autophagy dysfunction"],"prefix":"10.1371","volume":"22","author":[{"given":"Xiao","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University","place":["Yangling, Shaanxi, 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A&F University","place":["Yangling, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junying","family":"Xiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University","place":["Yangling, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9978-3030","authenticated-orcid":true,"given":"Xiangkai","family":"Leng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University","place":["Yangling, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Ultrasound in Cardiac Electrophysiology and Biomechanics Key Laboratory of Sichuan Province, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengke","family":"Pan","sequence":"additional","affiliation":[{"name":"Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People\u2019s Hospital","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengzhong","family":"Duan","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangwei","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University","place":["Yangling, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"issue":"7","key":"pgen.1012329.ref001","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41569-018-0007-y","article-title":"Mechanisms of physiological and pathological cardiac hypertrophy","volume":"15","author":"M Nakamura","year":"2018","journal-title":"Nat Rev Cardiol"},{"issue":"1","key":"pgen.1012329.ref002","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/s41572-025-00643-0","article-title":"Hypertrophic cardiomyopathy","volume":"11","author":"A Argir\u00f2","year":"2025","journal-title":"Nat 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