School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China; Department of Cardiothoracic Surgery, The Second Hospital of Anhui Medical University, Hefei 230601, PR China.
Department of Cardiothoracic Surgery, The Second Hospital of Anhui Medical University, Hefei 230601, PR China.
Cell Signal. 2020 Oct;74:109705. doi: 10.1016/j.cellsig.2020.109705. Epub 2020 Jul 4.
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.
长链非编码 RNA 生长停滞特异性转录本 5（LncRNA GAS5）参与纤维化疾病的形成。然而，LncRNA GAS5 在心脏纤维化发展中的关键作用仍不清楚。越来越多的证据表明，DNA 甲基化改变在心脏成纤维细胞激活中起核心作用。在本研究中，我们探讨了 MeCP2 失活导致 LncRNA GAS5 在心脏纤维化中表达下调。分析了 LncRNA GAS5 和 MeCP2 的增益和缺失功能。在心脏纤维化组织中，LncRNA GAS5 的表达显著降低，而 MeCP2 的表达显著增加。此外，TGF-β1 诱导的心脏成纤维细胞中 MeCP2 的表达增加，而 LncRNA GAS5 的表达减少。下调 LncRNA GAS5 导致细胞增殖增加。相反，外源性过表达 LncRNA GAS5 可抑制心脏成纤维细胞的增殖。5-AzadC 或敲低 MeCP2 处理可显著恢复心脏成纤维细胞中 LncRNA GAS5 的表达，而过表达 MeCP2 处理可显著抑制心脏成纤维细胞中 LncRNA GAS5 的表达。总之，这些结果表明，MeCP2 沉默触发了心脏纤维化中心脏成纤维细胞的激活。
