Open AccessCCAAT /enhancer‐binding protein β overexpression alleviates myocardial remodelling by regulating angiotensin‐converting enzyme‐2 expression in diabetes
Author(s) -
Tie Yuanyuan,
Zhai Chungang,
Zhang Ya,
Qin Xiaoteng,
Yu Fangpu,
Li Hongxuan,
Shan MeiRong,
Zhang Cheng
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13406
Subject(s) - ccaat enhancer binding proteins , diabetic cardiomyopathy , endocrinology , transcription factor , angiotensin ii , streptozotocin , medicine , cardiac fibrosis , downregulation and upregulation , angiotensin converting enzyme , diabetes mellitus , angiotensin converting enzyme 2 , chemistry , cardiomyopathy , biology , heart failure , microbiology and biotechnology , receptor , nuclear protein , biochemistry , disease , covid-19 , blood pressure , infectious disease (medical specialty) , gene
Diabetic cardiomyopathy, a major cardiac complication, contributes to heart remodelling and heart failure. Our previous study discovered that CCAAT /enhancer‐binding protein β (C/ EBP β), a transcription factor that belongs to a family of basic leucine zipper transcription factors, interacts with the angiotensin‐converting enzyme 2 ( ACE 2) promoter sequence in other disease models. Here, we aimed to determine the role of C/ EBP β in diabetes and whether ACE 2 expression is regulated by C/ EBP β. A type 1 diabetic mouse model was generated by an intraperitoneal injection of streptozotocin. Diabetic mice were injected with a lentivirus expressing either C/ EBP β or sh‐C/ EBP β or treated with valsartan after 12 weeks to observe the effects of C/ EBP β. In vitro , cardiac fibroblasts and cardiomyocytes were treated with high glucose ( HG ) to investigate the anti‐fibrosis, anti‐apoptosis and regulatory mechanisms of C/ EBP β. C/ EBP β expression was down‐regulated in diabetic mice and HG ‐induced cardiac neonatal cells. C/ EBP β overexpression significantly attenuated collagen deposition and cardiomyocyte apoptosis by up‐regulating ACE 2 expression. The molecular mechanism involved the binding of C/ EBP β to the ACE 2 promoter sequence. Although valsartan, a classic angiotensin receptor blocker, relieved diabetic complications, the up‐regulation of ACE 2 expression by C/ EBP β overexpression may exert greater beneficial effects on patients with diabetic cardiomyopathy.