{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:21:44Z","timestamp":1785410504238,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"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":"publisher","award":["82270914"],"award-info":[{"award-number":["82270914"]}],"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":["82070869"],"award-info":[{"award-number":["82070869"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82270914"],"award-info":[{"award-number":["82270914"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82070869"],"award-info":[{"award-number":["82070869"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>RNA degradation plays a vital role in post-transcriptional regulation of gene expression. RNA stability is changed in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD), but its role and underlying mechanisms in sleeve gastrectomy (SG) effectively remodeling hepatocytes and improving MASLD is unclear. A high-fat diet-induced MASLD model for SG and a hepatocyte-specific Zfp36 knockdown mouse model were established to evaluate the role of zinc finger protein 36 (ZFP36) in MASLD. The expression of ZFP36 and TEA domain transcription factor 4 (TEAD4) was examined in liver tissue samples from MASLD patients. Hepatic ZFP36 expression is downregulated in MASLD but is restored following SG. Hepatocyte-specific Zfp36 knockdown exacerbates high-fat diet-induced liver injury and impairs the therapeutic effect of SG on hepatic steatosis. Mechanistically, ZFP36 binds to TEAD4 mRNA to promote its degradation, thereby modulating the Hippo pathway. Inhibition of TEAD4 transcriptional activity reverses the aggravated MASLD phenotype caused by Zfp36 knockdown. In liver biopsy samples from MASLD patients, ZFP36 expression correlates negatively with TEAD4 expression. Collectively, these findings identify SG-induced upregulation of ZFP36 as a critical mechanism for alleviating MASLD through suppression of TEAD4.<\/jats:p>","DOI":"10.3390\/ijms27093736","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T08:11:14Z","timestamp":1776931874000},"page":"3736","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ZFP36 Alleviates MASLD Through Facilitating TEAD4 mRNA Degradation After Sleeve Gastrectomy"],"prefix":"10.3390","volume":"27","author":[{"given":"Zhiyuan","family":"Tang","sequence":"first","affiliation":[{"name":"Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Sun","sequence":"additional","affiliation":[{"name":"Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Shi","sequence":"additional","affiliation":[{"name":"Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3848-4589","authenticated-orcid":false,"given":"Tianming","family":"Yu","sequence":"additional","affiliation":[{"name":"Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanyuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1007\/s12072-024-10704-3","article-title":"Epidemiology and diagnosis of metabolic dysfunction-associated fatty liver disease","volume":"18","author":"Fouad","year":"2024","journal-title":"Hepatol. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1001\/jama.2020.2298","article-title":"Nonalcoholic Steatohepatitis: A Review","volume":"323","author":"Sheka","year":"2020","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/s41401-022-00860-3","article-title":"Updates on novel pharmacotherapeutics for the treatment of nonalcoholic steatohepatitis","volume":"43","author":"Yang","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1001\/jama.2020.14775","article-title":"Sleeve Gastrectomy","volume":"324","author":"Brajcich","year":"2020","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1016\/S0140-6736(23)00634-7","article-title":"Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): A multicentre, open-label, randomised trial","volume":"401","author":"Verrastro","year":"2023","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1053\/j.gastro.2020.06.006","article-title":"Bariatric Surgery Provides Long-term Resolution of Nonalcoholic Steatohepatitis and Regression of Fibrosis","volume":"159","author":"Lassailly","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1007\/s11427-023-2494-x","article-title":"RNA modifications in the progression of liver diseases: From fatty liver to cancer","volume":"67","author":"Li","year":"2024","journal-title":"Sci. China Life Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.molmed.2023.07.001","article-title":"Alternative splicing: A bridge connecting NAFLD and HCC","volume":"29","author":"Xu","year":"2023","journal-title":"Trends Mol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1016\/j.cmet.2021.09.008","article-title":"DRAK2 aggravates nonalcoholic fatty liver disease progression through SRSF6-associated RNA alternative splicing","volume":"33","author":"Li","year":"2021","journal-title":"Cell Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.ymthe.2021.09.016","article-title":"METTL3-m(6)A-Rubicon axis inhibits autophagy in nonalcoholic fatty liver disease","volume":"30","author":"Peng","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1840","DOI":"10.1002\/wrna.1840","article-title":"Emerging roles of RNA-binding proteins in fatty liver disease","volume":"15","author":"Adesanya","year":"2024","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13498","DOI":"10.1038\/ncomms13498","article-title":"CUG-binding protein 1 regulates HSC activation and liver fibrogenesis","volume":"7","author":"Wu","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41419-021-03514-0","article-title":"Hepatic HuR protects against the pathogenesis of non-alcoholic fatty liver disease by targeting PTEN","volume":"12","author":"Tian","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Makita, S., Takatori, H., and Nakajima, H. (2021). Post-Transcriptional Regulation of Immune Responses and Inflammatory Diseases by RNA-Binding ZFP36 Family Proteins. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.711633"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e2408811","DOI":"10.1002\/advs.202408811","article-title":"ZFP36 Regulates Vascular Smooth Muscle Contraction and Maintains Blood Pressure","volume":"12","author":"Cui","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1080\/15548627.2019.1687985","article-title":"RNA-binding protein ZFP36\/TTP protects against ferroptosis by regulating autophagy signaling pathway in hepatic stellate cells","volume":"16","author":"Zhang","year":"2020","journal-title":"Autophagy"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.tem.2018.04.006","article-title":"Hippo Signaling: Key Emerging Pathway in Cellular and Whole-Body Metabolism","volume":"29","author":"Ardestani","year":"2018","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.jhep.2021.09.032","article-title":"Dopamine receptor D2 antagonism normalizes profibrotic macrophage-endothelial crosstalk in non-alcoholic steatohepatitis","volume":"76","author":"Qing","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/s41575-021-00571-w","article-title":"Hippo signalling in the liver: Role in development, regeneration and disease","volume":"19","author":"Russell","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1146\/annurev-pathol-030420-105050","article-title":"The Hippo Pathway in Liver Homeostasis and Pathophysiology","volume":"16","author":"Driskill","year":"2021","journal-title":"Annu. Rev. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/s44320-024-00024-x","article-title":"Estrogen receptor activation remodels TEAD1 gene expression to alleviate hepatic steatosis","volume":"20","author":"Sommerauer","year":"2024","journal-title":"Mol. Syst. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1469","DOI":"10.1002\/wrna.1469","article-title":"Complex HuR function in pancreatic cancer cells","volume":"9","author":"Brody","year":"2018","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/s41574-021-00507-z","article-title":"Emerging therapeutic approaches for the treatment of NAFLD and type 2 diabetes mellitus","volume":"17","author":"Ferguson","year":"2021","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1016\/S0140-6736(20)32511-3","article-title":"Non-alcoholic fatty liver disease","volume":"397","author":"Powell","year":"2021","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.jhep.2018.10.033","article-title":"Non-alcoholic fatty liver disease\u2014A global public health perspective","volume":"70","author":"Younossi","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1001\/jama.2021.19569","article-title":"Association of Bariatric Surgery with Major Adverse Liver and Cardiovascular Outcomes in Patients with Biopsy-Proven Nonalcoholic Steatohepatitis","volume":"326","author":"Aminian","year":"2021","journal-title":"JAMA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4022","DOI":"10.1007\/s11695-018-3466-7","article-title":"Laparoscopic Sleeve Gastrectomy Resolves NAFLD: Another Formal Indication for Bariatric Surgery?","volume":"28","author":"Esquivel","year":"2018","journal-title":"Obes. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"155663","DOI":"10.1016\/j.metabol.2023.155663","article-title":"Uroguanylin prevents hepatic steatosis, mitochondrial dysfunction and fibrosis in obesity-associated NAFLD","volume":"147","author":"Losarcos","year":"2023","journal-title":"Metabolism"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.asjsur.2020.05.030","article-title":"Sleeve gastrectomy ameliorated high-fat diet (HFD)-induced non-alcoholic fatty liver disease and upregulated the nicotinamide adenine dinucleotide +\/Sirtuin-1 pathway in mice","volume":"44","author":"Hua","year":"2021","journal-title":"Asian J. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Jeong, S., Oh, M., Han, J., and Kim, S.K. (2025). RNA Degradation in Pluripotent Stem Cells: Mechanisms, Crosstalk, and Fate Regulation. Cells, 14.","DOI":"10.3390\/cells14201634"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"eabo0981","DOI":"10.1126\/sciimmunol.abo0981","article-title":"The ZFP36 family of RNA binding proteins regulates homeostatic and autoreactive T cell responses","volume":"7","author":"Cook","year":"2022","journal-title":"Sci. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41421-025-00784-2","article-title":"Senescence-induced p21(high) macrophages contributed to CD8(+) T cells-related immune hyporesponsiveness in kidney transplantation via Zfp36\/IL-27 axis","volume":"11","author":"Zhu","year":"2025","journal-title":"Cell Discov."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/s41419-024-06964-4","article-title":"Regulation of Zfp36 by ISGF3 and MK2 restricts the expression of inflammatory cytokines during necroptosis stimulation","volume":"15","author":"Yadav","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"112411","DOI":"10.1016\/j.celrep.2023.112411","article-title":"ZFP36-mediated mRNA decay regulates metabolism","volume":"42","author":"Cicchetto","year":"2023","journal-title":"Cell Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"112119","DOI":"10.1016\/j.cellsig.2025.112119","article-title":"ZFP36 reverses chemoresistance by disrupting lipid droplets accumulation in non-small cell lung cancer","volume":"136","author":"Wang","year":"2025","journal-title":"Cell Signal"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"156131","DOI":"10.1016\/j.metabol.2024.156131","article-title":"Adipose ZFP36 protects against diet-induced obesity and insulin resistance","volume":"164","author":"Hu","year":"2025","journal-title":"Metabolism"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"28177","DOI":"10.1038\/s41598-025-13477-3","article-title":"Identification of palmitoylated biomarkers in non-alcoholic fatty liver disease via integrated bioinformatics analysis and machine learning","volume":"15","author":"Liu","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1172\/JCI95802","article-title":"Hippo-mediated suppression of IRS2\/AKT signaling prevents hepatic steatosis and liver cancer","volume":"128","author":"Jeong","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.cmet.2020.03.010","article-title":"Cholesterol Stabilizes TAZ in Hepatocytes to Promote Experimental Non-alcoholic Steatohepatitis","volume":"31","author":"Wang","year":"2020","journal-title":"Cell Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.jhep.2021.04.033","article-title":"Dysregulation of the ESRP2-NF2-YAP\/TAZ axis promotes hepatobiliary carcinogenesis in non-alcoholic fatty liver disease","volume":"75","author":"Hyun","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4995","DOI":"10.1038\/s41467-024-49045-y","article-title":"The RNF214-TEAD-YAP signaling axis promotes hepatocellular carcinoma progression via TEAD ubiquitylation","volume":"15","author":"Lin","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"D1670","DOI":"10.1093\/nar\/gkae973","article-title":"Generic Diagramming Platform (GDP): A comprehensive database of high-quality biomedical graphics","volume":"53","author":"Jiang","year":"2025","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/3736\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T04:10:57Z","timestamp":1778127057000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/3736"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,22]]},"references-count":42,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27093736"],"URL":"https:\/\/doi.org\/10.3390\/ijms27093736","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,22]]}}}