MiR-155 regulates high glucose-induced cardiac fibrosis via the TGF-β signaling pathway.

Abstract

Cardiac fibrosis, as a pathological process, plays an important role in various cardiac diseases. microRNA-155 (miR-155) is one of the most important miRNAs, and previous studies have shown that it is a regulatory factor in various fibrotic diseases. However, the mechanism by which miR-155 affects myocardial fibrosis remains unclear. In this study, we aim to establish the biological function of miR-155 in myocardial fibrosis induced by diabetes in mice. We used normal C57BL/6 wild type (WT) and miR-155 knockout (KO) mice to establish the diabetic model by intraperitoneal injection of streptozotocin, and we utilized echocardiography to evaluate the cardiac function at 30 and 60 days post-modeling. Hematoxylin-eosin (HE) and sirius-red (SR) staining were used to evaluate the degree of myocardial lesions. Furthermore, we extracted cardiac fibroblasts (CFs) from the WT mice and transfected them with miR-155 inhibitors, mimics and negative control siRNAs to analyze the specific mechanism involved in the development of myocardial fibrosis. The results showed that miR-155 deficiency could prevent cardiac fibrosis induced by diabetes in mice and also that attenuated collagen synthesis is induced by high glucose (HG) in CFs. We found that miR-155 regulated cardiac fibrosis via the TGF-β1-Smad 2 signaling pathway. These findings suggest that miR-155 may be a therapeutic target for preventing cardiac fibrosis induced by diabetes.