Effect of DNMT3A Methylated LncRNA GAS5 on Myocardial Fibrosis - Abstract
Background: The main pathological manifestations of myocardial fibrosis are the proliferation of myocardial fibroblasts and the mass deposition of collagen fibers in myocardial tissue. It is a common feature of all cardiovascular diseases. Studies have shown that Lnc RNA can regulate myocardial fibrosis by regulating fibroblast proliferation, differentiation and collagen deposition through a variety of mechanisms. This study aims to investigate the expression and biological function of Lnc RNA GAS5 in myocardial fibrosis.
Methods: Animal models were constructed and the pathological changes of rat heart tissue were observed by HE, Masson and Sirius staining. The expressions of caspase1, NLRP3, DNMT3A and Col11 were analyzed by Western blot and q RT-PCR. Pyrodeath of target cells was detected by flow cytometry and Hoechst 33358 staining.After transient transfection of si DNMT3A, the expression of Lnc RNA GAS5 and its effect on pyrodeath of myocardial fibroblasts were recorded
Results: In this study, we identified LncRNA-GAS5 as the key onset of cardiac fibroblast pyroptosis and cardiac fibrosis. Here, we detected ISO-induced cardiac fibrosis models and cardiac fibroblast pyroptosis model. We found that the expression of pyroptosis-related proteins such as caspase 1, NLRP3, and DNMT1 was increased in cardiac fibrosis tissue, while the expression of GAS5 was decreased. The overexpressing of LncRNA GAS5 was shown to increase and inhibit cardiac fibroblast pyroptosis, as well as attenuate caspase 1 and NLRP3 expression in cardiac expression by reversion of promoter hypermethylation in cardiac fibroblast.
Conclusion: This study showed that DNMT3A methylation of LncRNA GAS5 leads to cardiac fibroblast pyroptosis via affecting NLRP3 axis. Our findings indicate a new regulatory mechanism for cardiac fibroblast pyroptosis, providing a novel therapeutic target for cardiac fibrosis.