MicroRNA29a Reverts the Activated Hepatic Stellate Cells in the Regression of Hepatic Fibrosis through Regulation of ATPase H⁺ Transporting V1 Subunit C1.

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 (PPARγ). 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. PPARγ 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 (α-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.

Citation

Fei Jing, Yan Geng, Xin-Yi Xu, Hong-Yu Xu, Jin-Song Shi, Zheng-Hong Xu. MicroRNA29a Reverts the Activated Hepatic Stellate Cells in the Regression of Hepatic Fibrosis through Regulation of ATPase H⁺ Transporting V1 Subunit C1. International journal of molecular sciences. 2019 Feb 13;20(4)

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PMID: 30781750

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