LncRNA GAS5 controls cardiac fibroblast activation and fibrosis by targeting miR-21 via PTEN/MMP-2 signaling pathway
LncRNA GAS5 controls cardiac fibroblast activation and fibrosis by targeting miR-21 via PTEN/MMP-2 signaling pathway
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LncRNA GAS5 通过 PTEN/MMP-2 信号通路靶向 miR-21 控制心脏成纤维细胞活化和纤维化
DOI：
10.1016/j.tox.2017.05.007
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发表时间：
2017-07-01
期刊：
影响因子：
4.5
通讯作者：
Shi, Kai-Hu
中科院分区：
文献类型：
--
作者：
Tao, Hui;Zhang, Jia-Gui;Shi, Kai-Hu
长非编码 RNA (LncRNA) 在包括心脏纤维化在内的许多疾病中异常表达。据报道，LncRNA 生长停滞特异性 5 (GAS5) 是控制细胞增殖和生长的重要介质；然而，其在心脏纤维化中的作用和功能仍不清楚。在这项研究中，我们证实GAS5在心脏纤维化组织以及活化的心脏成纤维细胞中低表达。 GASS 的过表达抑制了心脏成纤维细胞的增殖。此外，据报道，microRNA-21 (miR-21) 在心脏纤维化组织以及活化的心脏成纤维细胞中过度表达，这负责心脏纤维化的进展。我们发现上调 GAS5 显着降低 miR-21 的表达。此外，GAS5通过miR-21上调或下调心脏成纤维细胞中PTEN的表达。综上所述，GAS5 通过负调节 miR-21 在心脏纤维化中发挥抑制作用。这些结果表明GAS5可能成为进一步研究心脏纤维化的新治疗靶点。
Long noncoding RNAs (LncRNAs) are aberrantly expressed in many diseases including cardiac fibrosis. LncRNA growth arrest-specific 5 (GAS5) is reported as a significant mediator in the control of cell proliferation and growth; however, the role and function in cardiac fibrosis remain unknown. In this study, we confirmed that GAS5 was lowly expressed in cardiac fibrosis tissues as well as activated cardiac fibroblast. Overexpression of GASS inhibited the proliferation of cardiac fibroblast. Moreover, microRNA-21 (miR-21) has been reported to be overexpressed in cardiac fibrosis tissues as well as activated cardiac fibroblast, which is responsible for the progression of cardiac fibrosis. We found that up-regulated GAS5 decreased the expression of miR-21 significantly. Furthermore, GAS5 that upregulated or downregulated the expression of PTEN through miR-21 in cardiac fibroblasts. Taken together, GAS5 plays a suppressive role in cardiac fibrosis via negative regulation of miR-21. These results indicated that GAS5 may be a novel therapeutic target for further research of cardiac fibrosis.