{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:53:02Z","timestamp":1780635182624,"version":"3.54.1"},"reference-count":0,"publisher":"American Diabetes Association","license":[{"start":{"date-parts":[[2023,3,11]],"date-time":"2023-03-11T00:00:00Z","timestamp":1678492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Heat shock protein 20 (HSP20) emerges as a novel regulator of autophagy in the heart. Nonetheless, the detailed function of HSP20 in liver and its effect on autophagy remain unknown. Here, we observed that HSP20 expression is increased in liver tissues from mice and patients with metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD). Liver-specific downregulation of HSP20 mitigates hepatic steatosis and insulin resistance in obese mice, while upregulating HSP20 promotes lipid deposition and hepatocyte cell death. Mechanistically, Liquid chromatography tandem mass spectrometry (LC-MS\/MS) revealed that HSP20 interacts with phosphorylated extracellular regulated protein kinases 2 (ERK2) and prevents its dephosphorylation by dual specificity phosphatase 6 (DUSP6), leading to ERK2-mediated repression of autophagy, resulting in aggravated saturated fatty acid (SFA)-triggered hepatocyte death. Importantly, such adverse effects could be ameliorated by ERK inhibitor. Our data reveals a framework of how HSP20 increases susceptibility of SFA-induced liver injury through enhancing ERK2 phosphorylation, which represents a plausible therapeutic intervention to combat MASLD.<\/jats:p>","DOI":"10.2337\/db23-0688","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T18:49:56Z","timestamp":1710182996000},"update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":2,"title":["Inhibition of HSP20 ameliorates steatotic liver disease by stimulating ERK2-dependent autophagy"],"prefix":"10.2337","author":[{"given":"Yanli","family":"Miao","sequence":"first","affiliation":[{"name":"1Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China."},{"name":"2Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."},{"name":"3Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhong","sequence":"additional","affiliation":[{"name":"3Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."},{"name":"5Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutian","family":"Li","sequence":"additional","affiliation":[{"name":"4Department of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojie","family":"Qin","sequence":"additional","affiliation":[{"name":"2Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."},{"name":"3Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Yang","sequence":"additional","affiliation":[{"name":"5Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojun","family":"Cao","sequence":"additional","affiliation":[{"name":"6Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Tang","sequence":"additional","affiliation":[{"name":"6Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Yu","sequence":"additional","affiliation":[{"name":"7Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Fan","sequence":"additional","affiliation":[{"name":"2Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."},{"name":"3Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Lu1","sequence":"additional","affiliation":[{"name":"1Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangtong","family":"Peng","sequence":"additional","affiliation":[{"name":"2Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."},{"name":"3Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Huang","sequence":"additional","affiliation":[{"name":"2Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."},{"name":"3Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."},{"name":"8Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology, Wuhan, China."},{"name":"9Hubei clinical research center of metabolic and cardiovascular disease, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2024,3,11]]},"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/doi\/10.2337\/db23-0688\/749557\/db230688.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/doi\/10.2337\/db23-0688\/749557\/db230688.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T18:49:57Z","timestamp":1710182997000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/doi\/10.2337\/db23-0688\/154322\/Inhibition-of-HSP20-ameliorates-steatotic-liver"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,11]]},"references-count":0,"URL":"https:\/\/doi.org\/10.2337\/db23-0688","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,11]]},"article-number":"db230688"}}