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Micro RNA ‐145 regulates disabled‐2 and Wnt3a expression in cardiomyocytes under hyperglycaemia
Author(s) -
Wang BaoWei,
Fang WeiJen,
Shyu KouGi
Publication year - 2018
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.12867
Subject(s) - endocrinology , medicine , diabetic cardiomyopathy , downregulation and upregulation , wnt signaling pathway , angiotensin ii , messenger rna , streptozotocin , wnt3a , gene knockdown , gene expression , catenin , microrna , diabetes mellitus , chemistry , biology , apoptosis , microbiology and biotechnology , signal transduction , heart failure , cardiomyopathy , gene , biochemistry , blood pressure
Aims Micro RNA ‐145 (miR‐145) could protect cardiomyocyte apoptosis against oxidative stress and repair infarcted myocardium. Angiotensin II (Ang II ), a pro‐inflammatory cytokine could modulate myocardial remodelling. However, the role of hyperglycaemia on miR‐145 expression in cardiomyocyte or diabetes is not known. The effect of Ang II on miR‐145 expression under hyperglycaemia in cardiomyocytes remains unknown. We sought to investigate the effect of hyperglycaemia and Ang II on miR‐145 expression in cardiomyocytes. Methods Rat cardiomyocytes were cultured under high glucose concentration (25 mmol/L), and streptozotocin‐induced diabetic rats were established. TaqMan ® Micro RNA real‐time quantitative assay was used to quantitate miR‐145. Results Sustained high glucose concentration (hyperglycaemia) significantly decreased miR‐145 expression in cardiomyocytes. Hyperglycaemia significantly increased Ang II mRNA expression and secretion from rat cardiomyocytes. Ang II suppressed miR‐145 expression in cardiomyocytes. Hyperglycaemia increased Dab2 and decreased Wnt3a/ß‐catenin expression in cardiomyocytes. Repression of miR‐145 expression by Ang II resulted in increased Dab2 and decreased Wnt3a and ß‐catenin expression under hyperglycaemia. In contrast, overexpression of miR‐145 significantly decreased Dab2 mRNA and protein expression, whereas the mRNA and protein levels for Wnt3a and ß‐catenin were significantly reduced in left ventricular myocardium from 5 days to 28 days in diabetic rats. The protein expression patterns of Dab2 and Wnt3a/ß‐catenin in left ventricular myocardium of diabetic rats could be reversed upon treatment with valsartan. Conclusions Ang II downregulates miR‐145 to regulate Dab2 and Wnt3a/ß‐catenin expression in cardiomyocytes under high glucose concentration. Ang II plays a critical role in the regulation of miR‐145 in cardiomyocytes under hyperglycaemic conditions.