Inhibition of miR-543 alleviates cardiac fibroblast-to-myofibroblast transformation and collagen expression in insulin resistance via targeting PTEN.

Myocardial interstitial fibrosis is an important manifestation of diabetic heart disease, and insulin resistance is one of the mechanisms of myocardial interstitial fibrosis. Some studies have found that miR-543 is associated with insulin resistance, but whether it plays a role in diabetic myocardial interstitial fibrosis remains unclear. This study aimed to investigate the role of miR-543 in diabetic myocardial interstitial fibrosis. The combination of high glucose and high insulin was used to establish an insulin-resistant myocardial fibroblast model. The expression levels of miR-543, α-SMA, collagen Ⅰ, collagen Ⅲ and PTEN were detected. Cell proliferation and migration were detected. Luciferase reporter gene assay was used to verify the targeting relationship between miR-543 and PTEN. The expression of miR-543 was up-regulated in myocardial fibroblasts with insulin resistance, which was consistent with the results of bioinformatics analysis. The proliferation and migration levels of myocardial fibroblasts in insulin-resistant states were increased, and the expression levels of α-SMA, collagen Ⅰ and collagen Ⅲ were also increased. Inhibition of miR-543 expression could reverse the above changes. Target gene prediction and dual luciferase reporter assay demonstrated that miR-543 could bind to the 3′UTR region of PTEN. Moreover, the effect of miR-543 on insulin-resistant myocardial fibroblasts is mediated by targeting PTEN. Inhibition of miR‐543 can reduce myocardial fibroblast-myofibroblast transformation and collagen expression in insulin-resistant states by targeting PTEN. • MiR-543 is significantly increased in insulin-resistant cardiac fibroblasts. • MiR-543 regulates myocardial fibroblast transformation and collagen expression by PTEN. • MiR-543 targets PTEN by binding to the 3′UTR region of PTEN. [ABSTRACT FROM AUTHOR]