Dataset Information

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

ABSTRACT: 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 CCl?-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.

SUBMITTER: Jing F

PROVIDER: S-EPMC6412626 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Jing Fei F Geng Yan Y Xu Xin-Yi XY Xu Hong-Yu HY Shi Jin-Song JS Xu Zheng-Hong ZH

International journal of molecular sciences 20190213 4

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 <i>MicroRNA29a (Mir29a)</i> in the resolution of liver fibrosis. <i>Mir29a</i> and lipid-related genes were up-regulated after the recovery ...[more]

PMID: 30781750

Similar Datasets

Project description:BackgroundLiver fibrosis is characterized by the excessive formation and accumulation of matrix proteins as a result of wound healing in the liver. A main event during fibrogenesis is the activation of the liver resident quiescent hepatic stellate cell (qHSC). Recent studies suggest that reversion of the activated HSC (aHSC) phenotype into a quiescent-like phenotype could be a major cellular mechanism underlying fibrosis regression in the liver, thereby offering new therapeutic perspectives for the treatment of liver fibrosis. Whether human HSCs have the ability to undergo a similar reversion in phenotype is currently unknown. The aim of the present study is to identify experimental conditions that can revert the in vitro activated phenotype of primary human HSCs and consequently to map the molecular events associated with this reversion process by gene expression profiling.ResultsWe find that epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2) synergistically downregulate the expression of ACTA2 and LOX in primary human aHSCs. Their combination with oleic acid, palmitic acid, and retinol further potentiates a more quiescent-like phenotype as demonstrated by the abundant presence of retinyl ester-positive intra-cytoplasmic lipid droplets, low expression levels of activation markers, and a reduced basal as well as cytokine-stimulated proliferation and matrix metalloproteinase activity. Gene expression profiling experiments reveal that these in vitro reverted primary human HSCs (rHSCs) display an intermediary phenotype that is distinct from qHSCs and aHSCs. Interestingly, this intermediary phenotype is characterized by the increased expression of several previously identified signature genes of in vivo inactivated mouse HSCs such as CXCL1, CXCL2, and CTSS, suggesting also a potential role for these genes in promoting a quiescent-like phenotype in human HSCs.ConclusionsWe provide evidence for the ability of human primary aHSCs to revert in vitro to a transitional state through synergistic action of EGF, FGF2, dietary fatty acids and retinol, and provide a first phenotypic and genomic characterization of human in vitro rHSCs.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets