{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T09:02:18Z","timestamp":1788339738490,"version":"build-2803163510"},"reference-count":59,"publisher":"Portland Press Ltd.","issue":"6","license":[{"start":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T00:00:00Z","timestamp":1584316800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,3,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Diabetic cardiac fibrosis increases ventricular stiffness and facilitates the occurrence of diastolic dysfunction. Retinoid X receptor (RXR) plays an important role in cardiac development and has been implicated in cardiovascular diseases. In the present study, we investigated the effects of RXR agonist treatment on streptozotocin (STZ)-induced diabetic cardiomyopathy (DCM) and the underlying mechanism. Sprague\u2013Dawley (SD) rats induced by STZ injection were treated with either RXR agonist bexarotene (Bex) or vehicle alone. Echocardiography was performed to determine cardiac structure and function. Cardiac fibroblasts (CFs) were treated with high glucose (HG) with or without the indicated concentration of Bex or the RXR ligand 9-cis-retinoic acid (9-cis-RA). The protein abundance levels were measured along with collagen, body weight (BW), blood biochemical indexes and transforming growth factor-\u03b2 (TGF-\u03b2) levels. The effects of RXR\u03b1 down-regulation by RXR\u03b1 small interfering RNA (siRNA) were examined. The results showed that bexarotene treatment resulted in amelioration of left ventricular dysfunction by inhibiting cardiomyocyte apoptosis and myocardial fibrosis. Immunoblot with heart tissue homogenates from diabetic rats revealed that bexarotene activated liver kinase B1 (LKB1) signaling and inhibited p70 ribosomal protein S6 kinase (p70S6K). The increased collagen levels in the heart tissues of DCM rats were reduced by bexarotene treatment. Treatment of CFs with HG resulted in significantly reduced LKB1 activity and increased p70S6K activity. RXR\u03b1 mediated the antagonism of 9-cis-RA on HG-induced LKB1\/p70S6K activation changes in vitro. Our findings suggest that RXR agonist ameliorates STZ-induced DCM by inhibiting myocardial fibrosis via modulation of the LKB1\/p70S6K signaling pathway. RXR agonists may serve as novel therapeutic agents for the treatment of DCM.<\/jats:p>","DOI":"10.1042\/cs20190985","type":"journal-article","created":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T10:30:30Z","timestamp":1584354630000},"page":"609-628","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Retinoid X receptor agonists attenuates cardiomyopathy in streptozotocin-induced type 1 diabetes through LKB1-dependent anti-fibrosis effects"],"prefix":"10.1042","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9477-9956","authenticated-orcid":false,"given":"Dajun","family":"Chai","sequence":"first","affiliation":[{"name":"Cardiovascular Department, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Lin","sequence":"additional","affiliation":[{"name":"Echocardiological Department, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaowen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, Fuqing City Hospital, Fuzhou 350005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changsheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Xie","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinyun","family":"Ruan","sequence":"additional","affiliation":[{"name":"Echocardiological Department, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxiu","family":"Lin","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy College, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhang","family":"Zeng","sequence":"additional","affiliation":[{"name":"School of Pharmacy College, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2020,3,24]]},"reference":[{"key":"2021113011105930400_B1","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1007\/s12020-012-9623-1","article-title":"A new insight of mechanisms, diagnosis and treatment of diabetic cardiomyopathy","volume":"41","author":"Zhang","year":"2012","journal-title":"Endocrine"},{"key":"2021113011105930400_B2","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.phrs.2011.05.009","article-title":"Nitric oxide, a janus-faced therapeutic target for diabetic microangiopathy-friend or foe?","volume":"64","author":"Yamagishi","year":"2011","journal-title":"Pharmacol. 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