{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T03:35:57Z","timestamp":1785900957140,"version":"3.56.0"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,6,5]],"date-time":"2017-06-05T00:00:00Z","timestamp":1496620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008903","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["MOHW106\u2010TDU\u2010B\u2010212\u2010113004"],"award-info":[{"award-number":["MOHW106\u2010TDU\u2010B\u2010212\u2010113004"]}],"id":[{"id":"10.13039\/100008903","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:sec><jats:label\/><jats:p>Hypertension\u2010induced cardiac hypertrophy and apoptosis are major characteristics of early\u2010stage heart failure (HF). Inhibition of extracellular signal\u2010regulated kinases (ERK) efficaciously suppressed angiotensin II (ANG II)\u2010induced cardiomyocyte hypertrophy and apoptosis by blocking insulin\u2010like growth factor II receptor (IGF\u2010IIR) signaling. However, the detailed mechanism by which ANG II induces ERK\u2010mediated IGF\u2010IIR signaling remains elusive. Here, we found that ANG II activated ERK to upregulate IGF\u2010IIR expression via the angiotensin II type I receptor (AT<jats:sub>1<\/jats:sub>R). ERK activation subsequently phosphorylates HSF1 at serine 307, leading to a secondary phosphorylation by glycogen synthase kinase III (GSK3) at serine 303. Moreover, we found that ANG II mediated ERK\/GSK3\u2010induced IGF\u2010IIR protein stability by downregulating the E3 ubiquitin ligase of IGF\u2010IIR RING finger protein CXXVI (RNF126). The expression of RNF126 decreased following ANG II\u2010induced HSF1<jats:sup>S303<\/jats:sup> phosphorylation, resulting in IGF\u2010IIR protein stability and increased cardiomyocyte injury. Inhibition of GSK3 significantly alleviated ANG II\u2010induced cardiac hypertrophy in vivo and in vitro. Taken together, these results suggest that HSF1 phosphorylation stabilizes IGF\u2010IIR protein stability by downregulating RNF126 during cardiac hypertrophy. ANG II activates ERK\/GSK3 to phosphorylate HSF1, resulting in RNF126 degradation, which stabilizes IGF\u2010IIR protein expression and eventually results in cardiac hypertrophy. HSF1 could be a valuable therapeutic target for cardiac diseases among hypertensive patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.25945","type":"journal-article","created":{"date-parts":[[2017,4,6]],"date-time":"2017-04-06T18:00:00Z","timestamp":1491501600000},"page":"979-989","source":"Crossref","is-referenced-by-count":34,"title":["HSF1 phosphorylation by ERK\/GSK3 suppresses RNF126 to sustain IGF\u2010IIR expression for hypertension\u2010induced cardiomyocyte hypertrophy"],"prefix":"10.1002","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0266-3233","authenticated-orcid":false,"given":"Chih\u2010Yang","family":"Huang","sequence":"first","affiliation":[{"name":"Translation Research Core, China Medical University Hospital China Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fa\u2010Lun","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate Institute of Basic Medical Science China Medical University Taichung"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu\u2010Fen","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology China Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan\u2010Ho","family":"Lin","sequence":"additional","affiliation":[{"name":"Emergency Department China Medical University Hospital Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray\u2010Jade","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, College of Medicine Taipei Medical University Taipei"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung\u2010Jung","family":"Ho","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine China Medical University Taichung Taiwan"},{"name":"Chinese Medicine Department China Medical University Beigang Hospital Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu\u2010Jen","family":"Tsai","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine China Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijaya V.","family":"Padma","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Bharathiar University Coimbatore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Wen","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology China Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih\u2010Yang","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Basic Medical Science China Medical University Taichung"},{"name":"School of Chinese Medicine China Medical University Taichung Taiwan"},{"name":"Department of Health and Nutrition Biotechnology Asia University Taichung"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.23.6341"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2016.00053"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1677\/JME-08-0121"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms161126067"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.48.30847"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0975"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.86.3.255"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2945"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00921.2003"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.4149\/endo_2013_01_39"},{"key":"e_1_2_7_12_1","first-page":"1","article-title":"Mitochondrial ROS\u2010induced ERK1\/2 activation and HSF2\u2010mediated AT1 R upregulation are required for doxorubicin\u2010induced cardiotoxicity","volume":"9999","author":"Huang C. 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