» Articles » PMID: 28091538

MircoRNA-145 Promotes Activation of Hepatic Stellate Cells Via Targeting Krüppel-like Factor 4

Overview
Journal Sci Rep
Specialty Science
Date 2017 Jan 17
PMID 28091538
Citations 12
Authors
Affiliations
Soon will be listed here.
Abstract

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.

Citing Articles

The miR-3074/BMP7 axis regulates TGF-β-caused activation of hepatic stellate cells in vitro and CCl-caused murine liver fibrosis in vivo.

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.


References
1.
Wen M, Men R, Liu X, Yang L . Involvement of miR-30c in hepatic stellate cell activation through the repression of plasminogen activator inhibitor-1. Life Sci. 2016; 155:21-8. DOI: 10.1016/j.lfs.2016.04.034. View

2.
Naito Y, Sakamoto N, Oue N, Yashiro M, Sentani K, Yanagihara K . MicroRNA-143 regulates collagen type III expression in stromal fibroblasts of scirrhous type gastric cancer. Cancer Sci. 2013; 105(2):228-35. PMC: 4317817. DOI: 10.1111/cas.12329. View

3.
Schuppan D, Kim Y . Evolving therapies for liver fibrosis. J Clin Invest. 2013; 123(5):1887-901. PMC: 3635731. DOI: 10.1172/JCI66028. View

4.
Guo C, Pan Q, Li D, Sun H, Liu B . miR-15b and miR-16 are implicated in activation of the rat hepatic stellate cell: An essential role for apoptosis. J Hepatol. 2009; 50(4):766-78. DOI: 10.1016/j.jhep.2008.11.025. View

5.
Lin Z, Chu H, Yen Y, Lewis B, Chen Y . Krüppel-like factor 4, a tumor suppressor in hepatocellular carcinoma cells reverts epithelial mesenchymal transition by suppressing slug expression. PLoS One. 2012; 7(8):e43593. PMC: 3427336. DOI: 10.1371/journal.pone.0043593. View