LncRNA GAS5 exacerbates renal tubular epithelial fibrosis by acting as a competing endogenous RNA of miR-96-5p
LncRNA GAS5 exacerbates renal tubular epithelial fibrosis by acting as a competing endogenous RNA of miR-96-5p
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LncRNA GAS5 通过作为 miR-96-5p 的竞争性内源 RNA 加剧肾小管上皮纤维化
DOI：
10.1016/j.biopha.2019.109411
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发表时间：
2020-01-01
影响因子：
7.5
通讯作者：
Xue, Yao-ming
中科院分区：
文献类型：
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作者：
Wang, Wei;Jia, Yi-jie;Xue, Yao-ming
肾纤维化是各种肾脏疾病的核心，包括糖尿病肾病（DKD）。长链非编码 RNA (lncRNA) 是调节肾纤维化的已知参与者。然而，它们在 DKD 中的表达和功能仍需阐明。本研究的目的是评估lncRNA GAS5如何调节TGF-β1处理的肾近端小管细胞的纤维化及其机制。在这项研究中，lncRNA GAS5 在 TGF-β1 处理的 HK-2 细胞和 HDF/STZ 小鼠的肾脏中均上调。 GAS5 的敲低可缓解肾小管上皮纤维化。这种效应是通过 miR-96-5p 的下调和功能失活介导的。此外，miR-96-5p在DKD小鼠中下调，这种下调减弱了FN1（纤连蛋白，FN）的抑制并导致其上调。 miR-96-5p 的减少部分归因于 GAS5 的 miRNA 海绵作用。我们的研究表明，lncRNA GAS5 的敲低通过竞争性结合 miR-96-5p 来抑制 FN1 的表达，从而导致抗纤维化。这些结果表明，靶向 lncRNA GAS5 可能是预防 DKD 的一种有前景的治疗策略。
Renal fibrosis is at the core of various renal diseases, including diabetic kidney disease (DKD). Long noncoding RNAs (lncRNAs) are known players in the regulation of renal fibrosis. However, their expression and function in DKD still need to be elucidated. The purpose of this study was to assess how lncRNA GAS5 regulates fibrosis and its mechanism in TGF-beta 1-treated renal proximal tubular cell. In this study, the lncRNA GAS5 was upregulated in both TGF-beta 1-treated HK-2 cells and the kidneys of HDF/STZ mice. Knockdown of GAS5 relieved renal tubular epithelial fibrosis. This effect was mediated by the downregulation and functional inactivation of miR-96-5p. Furthermore, miR-96-5p was downregulated in DKD mice, and this downregulation attenuated the repression of FN1(fibronectin, FN) and led to its upregulation. The decrease in miR-96-5p was partially attributed to the miRNA-sponge action of GAS5. Our research demonstrates that knockdown of lncRNA GAS5 leads to antifibrosis by competitively binding miR-96-5p, which inhibits the expression of FN1. These results indicate that targeting lncRNA GAS5 may be a promising therapeutic strategy for preventing DKD.