MicroRNA‑200a suppresses epithelial‑to‑mesenchymal transition in rat hepatic stellate cells via GLI family zinc finger 2

Yu,Fujun; Zheng,Yihu; Hong,Weilong; Chen,Bicheng; Dong,Peihong; Zheng,Jianjian

doi:10.3892/mmr.2015.4452

MicroRNA‑200a suppresses epithelial‑to‑mesenchymal transition in rat hepatic stellate cells via GLI family zinc finger 2

Authors:
- Fujun Yu
- Yihu Zheng
- Weilong Hong
- Bicheng Chen
- Peihong Dong
- Jianjian Zheng
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Affiliations: Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: October 16, 2015 https://doi.org/10.3892/mmr.2015.4452
Pages: 8121-8128

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Abstract

Hepatic stellate cells (HSCs) have an important role in liver fibrosis. Epithelial‑to‑mesenchymal transition (EMT), which is promoted by the Hedgehog (Hh) signaling pathway, is involved in the activation of HSCs. MicroRNAs (miRNAs/miRs) have been reported to be involved in the progression of liver fibrosis. A previous study indicated that the activation of HSCs was suppressed by miR‑200a via targeting transforming growth factor‑β2 and β‑catenin. However, whether miR‑200a is able to regulate the EMT in HSCs has remained elusive. The present study revealed that miR‑200a was decreased in vitro and in vivo during liver fibrosis. Furthermore, miR‑200a overexpression resulted in the inhibition of proliferation, α‑SMA expression and extracellular matrix production of activated HSCs. Of note, miR‑200a overexpression reduced myofibroblastic markers, including α‑SMA, type I collagen and desmin, and increased the epithelial cell marker E‑cadherin. These results were further confirmed by immunofluorescence staining. Further study showed that the expression of genes associated with Hh signaling, including Hhip, Shh and Gli1, were not affected by miR‑200a. However, Gli2, a downstream signaling protein of the Hh pathway, was inhibited by miR‑200a and confirmed as a target of miR‑200a using a dual luciferase reporter assay. In addition, the inhibition of the Hh pathway by miR‑200a resulted in an increase of BMP‑7 and Id2 as well as a reduction of Snai1 and S100A4. Collectively, the results of the present study demonstrated that miR‑200a suppressed the EMT process in HSCs, at least in part, via Gli2.

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