MicroRNA-122-5p prevents proliferation and promotes apoptosis of hepatic stellate cells by suppressing the cellular-Abelsongene/histone deacetylases 2 pathway
Open Access
- 1 January 2022
- journal article
- research article
- Published by SAGE Publications in Human & Experimental Toxicology
Abstract
Liver fibrosis is a wound-healing response and the activation of the hepatic stellate cell (HSC) is the core of hepatic fibrosis. MicroRNAs (miRNAs) participate in the development of fibrosis. It is reported that histone deacetylases (HDAC2) tyrosine phosphorylation by cellular-Abelsongene (c-Abl) induces malignant growth of cells. Here, we investigated the effect of miR-122-5p on the proliferation and apoptosis of HSCs. Normal human HSC line LX-2 and LX-2 cells stimulated by transforming growth factor (TGF)-beta 1 for 24 h were cultured and assigned into the blank group and the TGF-beta 1 group. The miR-122-5p inhibitor and its negative control were transfected into LX-2 cells and miR-122-5p mimic and its negative control were transfected into LX-2 cells stimulated by TGF-beta 1. The result showed that miR-122-5p expression was decreased in TGF-beta 1-stimulated LX-2 cells. miR-122-5p overexpression reduced the mRNA and protein levels of collagen I and alpha-smooth muscle actin, inhibited cell proliferation, and accelerated cell apoptosis. miR-122-5p targeted c-Abl. Meanwhile, miR-122-5p overexpression inhibited HSC activation by suppressing the c-Abl/HDAC2 pathway. In summary, miR-122-5p overexpression exerted anti-fibrosis effect and inhibited HSC activation by suppressing the c-Abl/HDAC2 pathway.Keywords
This publication has 50 references indexed in Scilit:
- Reversibility of liver fibrosisClinics and Research in Hepatology and Gastroenterology, 2015
- Experimental models of liver fibrosisArchives of Toxicology, 2015
- miR-122 – A key factor and therapeutic target in liver diseaseJournal of Hepatology, 2015
- Potent inhibition of TGF-βsignaling pathway regulator Abl: potential therapeutics for hepatic fibrosisJournal of Receptors and Signal Transduction, 2014
- c-Abl Stabilizes HDAC2 Levels by Tyrosine Phosphorylation Repressing Neuronal Gene Expression in Alzheimer’s DiseaseMolecular Cell, 2014
- Pathogenesis of liver cirrhosisWorld Journal of Gastroenterology, 2014
- Hepatic and serum levels of miR-122 after chronic HCV-induced fibrosisJournal of Hepatology, 2012
- MicroRNA‐122 suppresses cell proliferation and induces cell apoptosis in hepatocellular carcinoma by directly targeting Wnt/β‐catenin pathwayLiver International, 2012
- Hepatic stellate cell (vitamin A‐storing cell) and its relative – past, present and futureCell Biology International, 2010
- Liver fibrosisJCI Insight, 2005