MicroRNA-212 activates hepatic stellate cells and promotes liver fibrosis via targeting SMAD7

Journal Article · Mon Jan 15 04:00:00 EST 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.01.019· OSTI ID:23127435

Zhu, Jie ^[1]; Zhang, Ziqiang ^[2]; Zhang, Yitong; Li, Wenshuai; Zheng, Wanwei ^[1]; others, and

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1. Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, 200040 (China)
2. Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 200040 (China)

Highlights: • miR-212 is confirmed to be involved in the progression of liver fibrosis. • miR-212 facilitated activation of hepatic stellate cells and TGF-β pathway. • SMAD7 is identified as a direct target of miR-212. There has been an increasing number of researches about microRNAs (miRNAs) in the progression of liver fibrosis from the point of their comprehensive functions in regulating the activation of hepatic stellate cells (HSCs). Among them, it has been reported that miR-212 is up-regulated in activated rat primary HSCs. However, its mechanism has not been determined yet. Here, we confirmed that the level of miR-212–3p was up-regulated in livers of carbon tetrachloride (CCl{sub 4})-treated mice compared with the normal control, which is a classical model of chronically damaged fibrotic liver. In vitro, we demonstrated that TGF-β, a master fibrogenic cytokine, could induce the level of miR-212. In turn, overexpression of miR-212 could induce the activation marker of HSC including α-smooth muscle actin (α-SMA) and collagens by activating TGF-β signaling pathway. Furthermore, SMAD7, a dominant suppressor of TGF-β pathway, was identified as a direct target of miR-212–3p. Our results indicate that miR-212–3p facilitates the activation of HSCs and TGF-β pathway by targeting SMAD7, highlighting that it can be served as a novel biomarker or therapeutic target for liver fibrosis.

• OSTI ID: 23127435
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 496; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACTIN
BIOLOGICAL MARKERS
COLLAGEN
FIBROSIS
LIVER
LYMPHOKINES
MICE
RATS