MiR-142-3p blocks TGF-ß-induced activation of hepatic stellate cells through targeting TGFßRI

To understand the contribution of miR-142-3p in the activation of hepatic stellate cells (HSCs) and liver fibrosis, and the underlying mechanism. We detected microRNAs expression profiles in quiescent and activated HSCs by microRNA-array, and performed qRT-PCR to validate these data in HSCs and plas...

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Bibliographic Details
Published in:Life sciences (1973) 2017-10, Vol.187, p.22
Main Authors: Yang, Xiaoxue, Dan, Xuelian, Men, Ruoting, Ma, Liping, Wen, Maoyao, Peng, Yong, Yang, Li
Format: Article
Language:English
Subjects:
Activation
Cirrhosis
Ectopic expression
Fibrosis
Gene expression
Hepatocytes
Liver
Liver cirrhosis
Markers
MicroRNAs
miRNA
Patients
Ribonucleic acid
RNA
Signal transduction
Signaling
Smad protein
Stellate cells
Studies
Western blotting
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Summary:To understand the contribution of miR-142-3p in the activation of hepatic stellate cells (HSCs) and liver fibrosis, and the underlying mechanism. We detected microRNAs expression profiles in quiescent and activated HSCs by microRNA-array, and performed qRT-PCR to validate these data in HSCs and plasma of cirrhosis patients. In vitro, the 3rd-5th passage HSCs was transfected with mir-142-3p mimics or stimulated with TGF β. The markers of HSCs activation (i.e. FN and a-SMA) were examined by qRT-PCR and western blotting, and cell viability was detected by MTT, colony formation assays respectively. In our study, we identified miR-142-3p as a novel regulator of HSCs activation and indicator of hepatic cirrhosis. We found that miR-142-3p was significantly reduced in activated HSCs, while TGFβRI was distinctly up-regulated in activated HSCs. Ectopic expression of miR-142-3p in activated HSCs inhibited cell viability as well as cell growth, and blocked HSCs activation, concomitant with decreased transdifferentiation markers (i.e. FN and α-SMA). Further, we confirmed that miR-142-3p was reduced upon TGF-β exposure, while diminishing TGF-β-Smad signaling pathway in turn by reducing TGFβRI expression in HSCs. Besides, the plasma level of miR-142-3p declined significantly in patients with hepatic cirrhosis. In conclusion, we demonstrated that miR-142-3p repressed TGF-β-Smad signaling pathway to prevent HSCs activation through directly targeting TGFβRI in HSCs.
ISSN:0024-3205
1879-0631