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BET-inhibition by JQ1 alleviates streptozotocin-induced diabetic cardiomyopathy.

Authors
  • Guo, Miao1
  • Wang, Hong-Xia2
  • Chen, Wen-Jun3
  • 1 Department of Geriatrics, Linyi People's Hospital, Linyi, Shandong, China. , (China)
  • 2 Department of Geriatrics, Linyi Jiaotong Hospital, Linyi, Shandong, China. , (China)
  • 3 Department of Oncology, Linyi People's Hospital, Linyi, Shandong, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Toxicology and Applied Pharmacology
Publisher
Elsevier
Publication Date
May 18, 2018
Volume
352
Pages
9–18
Identifiers
DOI: 10.1016/j.taap.2018.05.018
PMID: 29782963
Source
Medline
Keywords
License
Unknown

Abstract

Diabetic cardiomyopathy is a cascade of complex events leading to eventual heart failure in diabetes. JQ1, one of Bromodomain and extra-terminal domain (BET) protein inhibitors, has exerted therapeutic effects on cancer proliferation, inflammation and cardiovascular disease. Recently, JQ1 was reported to protect mice from bleomycin-induced lung fibrosis and reverse the fibrotic response in carbon tetrachloride-induced liver fibrosis. However, its role in diabetic cardiomyopathy remains to be clarified. Our results indicated that JQ1 treatment suppressed cardiac fibrosis and improved cardiac function in a STZ-induced diabetic mouse model. We further used both cardiofibroblasts and cardiomyocytes in vitro to investigate the protective mechanism of JQ1. JQ1 significantly suppressed hyperglycemia-induced cardiofibroblasts proliferation and migration, myofibroblast differentiation, and collagen production. Moreover, JQ1 reduced hyperglycemia-induced apoptosis of cardiomyocytes in vitro and in vivo. Mechanistically, JQ1 treatment could reverse the expression of Caveolin-1, which modulates transforming growth factor-β1 (TGF-β1) signaling in cardiofibroblasts and inhibits cardiomyocytes apoptosis. Our findings identify BET inhibitor JQ1 as promising agent for diabetic cardiomyopathy.

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