{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:18:14Z","timestamp":1789985894649,"version":"4.0.1"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,5,19]],"date-time":"2019-05-19T00:00:00Z","timestamp":1558224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,5,19]],"date-time":"2019-05-19T00:00:00Z","timestamp":1558224000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008903","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["MOHW107\u2010TDU\u2010B\u2010212\u2010123004"],"award-info":[{"award-number":["MOHW107\u2010TDU\u2010B\u2010212\u2010123004"]}],"id":[{"id":"10.13039\/100008903","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cardiotoxicity by doxorubicin hampers its therapeutic potential as an anticancer drug, but mechanisms leading to cardiotoxicity remain contentious. Through this study, the functional contribution of insulin\u2010like growth factor receptor type II \u03b1 (IGF\u2010IIR\u03b1) which is a novel stress\u2010inducible protein was explored in doxorubicin\u2010induced cardiac stress. Employing both in vitro H9c2 cells and in vivo transgenic rat models (SD\u2010TG [IGF\u2010IIR\u03b1]) overexpressing IGF\u2010IIR\u03b1 specifically in heart, we found that IGF\u2010IIR\u03b1 leads to cardiac structural abnormalities and functional perturbations that were severely aggravated by doxorubicin\u2010induced cardiac stress. Overexpression of IGF\u2010IIR\u03b1 leads to cumulative elevation of stress associated cardiac hypertrophy and apoptosis factors. There was a significant reduction of survival associated proteins p\u2010Akt and estrogen receptor \u03b2\/\u03b1, and abnormal elevation of cardiac hypertrophy markers such as atrial natriuretic peptide, cardiac troponin\u2010I, and apoptosis\u2010inducing agents such as p53, Bax, and cytochrome\n                    <jats:italic>C<\/jats:italic>\n                    , respectively. IGF\u2010IIR\u03b1 also altered the expressions of AT1R, ERK1\/2, and p38 proteins. Besides, IGF\u2010IIR\u03b1 also increased the reactive oxygen species production in H9c2 cells which were markedly aggravated by doxorubicin treatment. Together, we showed that IGF\u2010IIR\u03b1 is a novel stress\u2010induced protein that perturbed cardiac homeostasis and cumulatively exacerbated the doxorubicin\u2010induced cardiac injury that perturbed heart functions and ensuing cardiomyopathy.\n                  <\/jats:p>","DOI":"10.1002\/jcb.28957","type":"journal-article","created":{"date-parts":[[2019,5,19]],"date-time":"2019-05-19T03:17:58Z","timestamp":1558235878000},"page":"16956-16966","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Upregulation of IGF\u2010IIR\u03b1 intensifies doxorubicin\u2010induced cardiac damage"],"prefix":"10.1002","volume":"120","author":[{"given":"Sudhir","family":"Pandey","sequence":"first","affiliation":[{"name":"Graduate Institute of Biomedical Sciences College of Medicine, China Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2097-2240","authenticated-orcid":false,"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":"Tsung\u2010Jung","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Chinese Medicine Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University  Hualien Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Lan","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Pathology Changhua Christian Hospital  Changhua Taiwan"},{"name":"Department of Nursing and Management Jen\u2010Teh Junior College of Medicine  Miaoli Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia\u2010Yao","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Nursing Mei Ho University, Pingguang Road  Pingtung 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 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruey\u2010Lin","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Postbaccalaureate Chinese Medicine College of Chinese Medicine, China Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei\u2010Ying","family":"Pai","sequence":"additional","affiliation":[{"name":"Division of Cardiology China Medical University Hospital  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. 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