MircoRNA-145 Promotes Activation of Hepatic Stellate Cells Via Targeting Krüppel-like Factor 4
Authors
Affiliations
Krüppel-like Factor 4 (KLF4), a target gene of miR-145, can negatively regulate lung fibrosis. However, the potential role of KLF4 and miR-145 in hepatic stellate cells (HSCs) activation or in hepatic fibrosis keeps unclear. This study aims to characterize miR-145 and KLF4 in activated HSCs and liver cirrhotic, and the underlying molecular basis. miR-145 was significantly up-regulated, while KLF4 was dramatically down-regulated during the activation of rat primary HSCs and TGF-βtreated HSCs. Furthermore, miR-145 mimics induced and inhibition of miR-145 reduced α-SMA and COL-I expression in primary HSCs. Additionally, the mRNA and protein levels of KLF4 in the liver of cirrhotic patients and rats were significantly down-regulated. α-SMA and COL-I were increased after inhibition of KLF4 by specific shRNA in primary HSCs. Forced KLF4 expression led to a reduction of α-SMA and COL-I expression in HSCs. miR-145 promotes HSC activation and liver fibrosis by targeting KLF4.
Liu B, Xie X, Yang X, Dou C, Tang H, Liu J Hum Cell. 2024; 37(2):435-450.
PMID: 38218754 DOI: 10.1007/s13577-023-01017-y.
Serum microRNAs in Systemic Sclerosis, Associations with Digital Vasculopathy and Lung Involvement.
Wajda A, Walczyk M, Dudek E, Stypinska B, Lewandowska A, Romanowska-Prochnicka K Int J Mol Sci. 2022; 23(18).
PMID: 36142646 PMC: 9503032. DOI: 10.3390/ijms231810731.
An Update in Epigenetics in Metabolic-Associated Fatty Liver Disease.
Rodriguez-Sanabria J, Escutia-Gutierrez R, Rosas-Campos R, Armendariz-Borunda J, Sandoval-Rodriguez A Front Med (Lausanne). 2022; 8:770504.
PMID: 35087844 PMC: 8787199. DOI: 10.3389/fmed.2021.770504.
lncRNA MEG3 modulates hepatic stellate cell activation by sponging miR‑145 to regulate PPARγ.
Qin R, Huang W, Huang Y, Zhang Z, Su Y, Chen S Mol Med Rep. 2021; 25(1).
PMID: 34738631 PMC: 8600405. DOI: 10.3892/mmr.2021.12519.
Profiles of messenger RNAs and MicroRNAs in hypoxia-induced hepatic stellate cells.
Zhang L, Gao J, Zhou D, Wang X, Li J, Wang J Ann Transl Med. 2021; 9(18):1451.
PMID: 34734003 PMC: 8506783. DOI: 10.21037/atm-21-4215.