The targeted regulation of miR-26a on PTEN-PI3K/AKT signaling pathway in myocardial fibrosis after myocardial infarction

S. Zhang, R. Cui

Department of Cardiology, Heilongjiang provincial Hospital,Harbin, Heilongjiang, P.R. China. haiyanzhouzxc@163.com

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• Cardiology

OBJECTIVE: MiR-26a is involved in regulating myocardial remodeling and it is also related to organ fibrosis. Its role in myocardial fibrosis process is still controversy. As a definite target gene of miR-26a, phosphatase and tensin homology does on chromosome ten (PTEN) plays a role in regulating PTEN-PI3K/AKT signaling pathway. This study explored the function of miR-26a in regulating PTEN-PI3K/AKT signaling pathway, MMP-9 expression, and myocardial fibrosis after acute myocardial infarction (AMI).

MATERIALS AND METHODS: AMI model was established on Sprague-Dawley (SD) rats. Hydroxyproline, COL1A1, miR-26a, PTEN, p-AKT, and MMP-9 expressions in myocardial tissue at 1 week, 2 weeks, and 4 weeks after modeling were detected. Human cardiac fibroblasts (HCF) were cultured in vitro to detect miR-26a, PTEN, p-AKT, MMP-9, COL1A1, and α-SMA expressions in the process of myofibroblast differentiation (P1, P3, P5). HCF in P5 were transfected with miR-26a mimics or inhibitor to test miR-26a, PTEN, p-AKT, MMP-9, COL1A1, and α-SMA expressions.

RESULTS: Hydroxyproline, COL1A1, miR-26a, p-AKT, and MMP-9 overexpressed, while PTEN downregulated in myocardial tissue during the process of myocardial fibrosis after AMI. MiR-26a, PTEN, p-AKT, MMP-9, COL1A1, and α-SMA expression gradually enhanced, while PTEN declined, following the process of HCF differentiating into myofibroblast. MiR-26a elevation suppressed PTEN expression, and increased p-AKT, MMP-9, COL1A1, and α-SMA levels. MiR-26a reduction significantly upregulated PTEN level, weakened PI3K/AKT signaling pathway activity, and declined MMP-9, COL1A1, and α-SMA protein expression.

CONCLUSIONS: MiR-26a upregulation may play a role in myocardial fibrosis after AMI by suppressing PTEN, enhancing PI3K/AKT signaling pathway and MMP-9 levels.

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