Department of Cardiology, Heilongjiang provincial Hospital,Harbin, Heilongjiang, P.R. China.
Eur Rev Med Pharmacol Sci. 2018 Jan;22(2):523-531. doi: 10.26355/eurrev_201801_14205.
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).
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.
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.
MiR-26a upregulation may play a role in myocardial fibrosis after AMI by suppressing PTEN, enhancing PI3K/AKT signaling pathway and MMP-9 levels.
miR-26a 参与调节心肌重构，与器官纤维化也有关。它在心肌纤维化过程中的作用仍存在争议。作为 miR-26a 的明确靶基因，磷酸酶和张力蛋白同源物（PTEN）在调节 PTEN-PI3K/AKT 信号通路中发挥作用。本研究探讨了 miR-26a 在调节急性心肌梗死（AMI）后 PTEN-PI3K/AKT 信号通路、MMP-9 表达和心肌纤维化中的功能。
建立 Sprague-Dawley（SD）大鼠 AMI 模型。检测建模后 1 周、2 周和 4 周心肌组织中的羟脯氨酸、COL1A1、miR-26a、PTEN、p-AKT 和 MMP-9 表达。体外培养人心房成纤维细胞（HCF），检测肌成纤维细胞分化过程中（P1、P3、P5）miR-26a、PTEN、p-AKT、MMP-9、COL1A1 和α-SMA 的表达。P5 中的 HCF 转染 miR-26a 模拟物或抑制剂，检测 miR-26a、PTEN、p-AKT、MMP-9、COL1A1 和α-SMA 的表达。
AMI 后心肌纤维化过程中，心肌组织中羟脯氨酸、COL1A1、miR-26a、p-AKT 和 MMP-9 过度表达，而 PTEN 下调。HCF 分化为肌成纤维细胞时，miR-26a、PTEN、p-AKT、MMP-9、COL1A1 和α-SMA 的表达逐渐增强，而 PTEN 下降。miR-26a 升高抑制 PTEN 表达，增加 p-AKT、MMP-9、COL1A1 和α-SMA 水平。miR-26a 减少显著上调 PTEN 水平，减弱 PI3K/AKT 信号通路活性，降低 MMP-9、COL1A1 和α-SMA 蛋白表达。
miR-26a 通过抑制 PTEN、增强 PI3K/AKT 信号通路和 MMP-9 水平，在 AMI 后心肌纤维化中发挥作用。
