MicroRNA29a Reverts the Activated Hepatic Stellate Cells in the Regression of Hepatic Fibrosis through Regulation of ATPase H+ Transporting V1 Subunit C1
MicroRNA29a Reverts the Activated Hepatic Stellate Cells in the Regression of Hepatic Fibrosis through Regulation of ATPase H+ Transporting V1 Subunit C1
复制标题
MicroRNA29a 通过调节 ATPase H 转运 V1 亚基 C1 恢复肝纤维化消退过程中激活的肝星状细胞
DOI：
10.3390/ijms20040796
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发表时间：
2019-02-02
影响因子：
5.6
通讯作者：
Xu, Zheng-Hong
中科院分区：
文献类型：
--
作者：
Jing, Fei;Geng, Yan;Xu, Zheng-Hong
活化的肝星状细胞（aHSC）在肝纤维化中发挥关键作用。在纤维化消退过程中，aHSC 转化为失活细胞 (iHSC)，它们是静止的含脂质细胞，表达较高水平的脂质相关基因，例如过氧化物酶体增殖物激活受体 γ (PPAR)。在这里，我们研究了 MicroRNA29a (Mir29a) 在解决肝纤维化中的作用。 CCl4诱导的小鼠肝纤维化恢复后，Mir29a和脂质相关基因上调。 PPAR 激动剂罗格列酮 (RSG) 促进 aHSC 去分化为 iHSC，并上调人 HSC 细胞系 LX-2 中的 MIR29a 表达。 MIR29a模拟物在体外促进脂质相关基因的表达，同时降低纤维化相关基因的表达。 MIR29a 抑制剂表现出相反的效果。 ATPase H+ 转运 V1 亚基 C1 (Atp6v1c1) 在肝纤维化过程中增加，而在小鼠恢复后下调，并在 LX-2 细胞中受到 MIR29a 的负调节。 siRNA 敲低 ATP6V1C1 可降低 α-平滑肌肌动蛋白 (-SMA) 并增加脂质相关基因的表达。同时添加 MIR29a 模拟物和 ATP6V1C1 siRNA 进一步增加 RSG，促进脂质相关蛋白的体外表达。总的来说，MIR29a 在 aHSC 转分化过程中在解决肝纤维化方面发挥着重要作用，部分是通过调节 ATP6V1C1 来实现的。
Activated hepatic stellate cells (aHSCs) play a key role in liver fibrosis. During the regression of fibrosis, aHSCs are transformed into inactivated cells (iHSCs), which are quiescent lipid-containing cells and express higher levels of lipid-related genes, such as peroxisome proliferators-activated receptors gamma (PPAR). Here, we investigated the role of MicroRNA29a (Mir29a) in the resolution of liver fibrosis. Mir29a and lipid-related genes were up-regulated after the recovery of CCl4-induced liver fibrosis in mice. PPAR agonist rosiglitazone (RSG) promoted de-differentiation of aHSCs to iHSCs and up-regulated MIR29a expression in a human HSC cell line LX-2. MIR29a mimics in vitro promoted the expression of lipid-related genes, while decreased the expression of fibrosis-related genes. MIR29a inhibitor showed the reverse effects. ATPase H+ transporting V1 subunit C1 (Atp6v1c1) was increased in liver fibrosis, while down-regulated after the recovery in mice, and negatively regulated by MIR29a in LX-2 cells. Knockdown of ATP6V1C1 by siRNA decreased alpha-smooth muscle actin (-SMA) and increased lipid-related genes expression. Simultaneous addition of MIR29a mimics and ATP6V1C1 siRNA further increased RSG promoted expression of lipid-related proteins in vitro. Collectively, MIR29a plays an important role during the trans-differentiation of aHSCs in the resolution of liver fibrosis, in part, through regulation of ATP6V1C1.