Long non coding RNA growth arrest-specific transcript 5 (LncRNA GAS5) participate in the formation of fibrosis diseases. However, the key role of LncRNA GAS5 in the development of cardiac fibrosis remains unclear. Accumulating evidence suggests that DNA methylation alterations play a central role in cardiac fibroblast activation. In this study, we explored MeCP2 inactivation of LncRNA GAS5 leads to down regulation of LncRNA GAS5 expression in cardiac fibrosis. Gain and loss function of LncRNA GAS5 and MeCP2 was analyzed. The expression of LncRNA GAS5 was significantly decreased in cardiac fibrosis tissues, while MeCP2 was significantly increased. Moreover, the expression of MeCP2 was increased in TGF-β1 induced cardiac fibroblasts, while the expression of LncRNA GAS5 was decreased. Down regulation of LncRNA GAS5 resulted in increasing cellular proliferation. In contrast, exogenous over expression of LncRNA GAS5 in cardiac fibroblasts inhibited cell proliferation. 5-AzadC or knockdown of MeCP2 treatment significantly restored LncRNA GAS5 expression in cardiac fibroblasts, while over expression of MeCP2 treatment significantly inhibited LncRNA GAS5 expression in cardiac fibroblasts. In summary, these results suggested that MeCP2 silencing of LncRNA GAS5 triggers cardiac fibroblasts activation in cardiac fibrosis.
Keywords: Activation; Cardiac fibroblasts; Cardiac fibrosis; DNA methylation; LncRNA GAS5.
Copyright © 2020 Elsevier Inc. All rights reserved.