Oncotarget

Research Papers:

Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster

Xian-Yi Zeng, Yan-Qiong Zhang, Xiao-Min He, Lin-Yan Wan, Hu Wang, Yi-Ran Ni, Jie Wang, Jiang-Feng Wu and Chang-Bai Liu _

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Oncotarget. 2016; 7:86198-86210. https://doi.org/10.18632/oncotarget.13365

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Abstract

Xian-Yi Zeng1,2,4,*, Yan-Qiong Zhang2,5,*, Xiao-Min He2,4,*, Lin-Yan Wan1,2,3,4,5,*, Hu Wang1,2,3,4, Yi-Ran Ni2, Jie Wang2, Jiang-Feng Wu1,2,3,4,5, Chang-Bai Liu1,2,3,4,5

1The Institute of Cell Therapy, China Three Gorges University, Yichang, 443000, China

2Medical College, China Three Gorges University, Yichang, 443002, China

3The First People’s Hospital of Yichang, Hubei Yichang, 443000, China

4Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, 443002, China

5Institute of Liver Diseases, China Three Gorges University, Yichang, 443002, China

*These authors contributed equally to this work

Correspondence to:

Jiang-Feng Wu, email: [email protected]

Chang-Bai Liu, email: [email protected]

Keywords: hepatic fibrosis, TGF-β, BMP-7, miR-23b/27b cluster, siRNA

Received: September 24, 2016     Accepted: November 08, 2016     Published: November 15, 2016

ABSTRACT

The imbalance between transforming growth factor β and bone morphogenetic protein 7 signaling pathways is a critical step in promoting hepatic stellate cell activation during hepatic fibrogenesis. Gremlin1 may impair the balance. Something remains unclear about the regulatory mechanisms of gremlin1 action on hepatic stellate cell activation and hepatic fibrosis. In the current study, gremlin1 overexpression promotes activation of hepatic stellate cells. Knockdown of gremlin1 with siRNAs suppresses hepatic stellate cell activation and attenuates hepatic fibrosis in rat model. Our results also show that miR-23b/27b cluster members bind to 3′-untranslated region of gremlin1 resulting in reduction of transforming growth factor β, α-smooth muscle actin and collagenI α1/2 gene expression. Our findings suggest that gremlin1 promotes hepatic stellate cell activation and hepatic fibrogenesis through impairment of the balance between transforming growth factor β and bone morphogenetic protein 7 signaling pathways. The miR-23b/27b cluster suppresses activation of hepatic stellate cells through binding gremlin1 to rectify the imbalance.


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