lncRNA Vgll3 Regulates the Activated Proliferation of Mouse Myocardial Fibroblasts through TGF-β3-Related Pathway

BACKGROUND: Cardiac fibrosis is a risk factor leading to various cardiac diseases, and its mechanism has not been clarified. However, long noncoding RNA (lncRNA) can mediate the pathological process of cardiac fibrosis. OBJECTIVE: This study is aimed at determining the pathological role of lncRNA Vgll3 in cardiac fibrosis and explore its potential mechanism. METHODS: Myocardium fibroblasts (CFs) were isolated from mice and stimulated with angiotensin II (Ang-II). The expression of Vgll3 and transforming growth factor-β3 (TGF-β3) were detected by real-time fluorescence quantitative PCR (qPCR). Double luciferase reporter gene and western blot analysis (WB) were used to detect the effect of Vgll3 on TGF-β3 expression. The qPCR and WB were used to detect TGF-β3 pathway markers such as TGF-β3 and SMAD4, as well as cardiac fibrosis markers such as α-smooth muscle actin (α-SMA), fibronectin (Fn), and type I collagen (Col1). The proliferation of CFs in mice was analyzed by Cell Counting Kit-8 (CCK8) and 5-bromo-2-deoxyuracil (EdU) method. RESULTS: Upregulation of Vgll3 promoted the expression of TGF-β3 and its downstream molecules in mouse CFs, while silencing of Vgll3 inhibited the TGF-β3 pathway. Upregulation of Vgll3 significantly promoted the activation and proliferation of mouse CFs cells. It promoted the mRNA and protein levels of α-SMA, Fn, Col1, and Col3, while silencing the expression of Vgll3 had the opposite effect. The above effects of upregulation of Vgll3 were counteracted by TGF-β3 knockdown intervention. CONCLUSION: Vgll3 can promote the activation and proliferation of CFs in mice by activating TGF-β3-related pathway.