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Research on promoting liver fibrosis injury by the targeted regulation of miR-202 for HGF to activate HSC

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Abstract

Background

Liver fibrosis is the primary cause of liver cirrhosis and hepatocellular carcinoma and leads to considerable morbidity and mortality. Recent studies have shown that microRNAs are associated with fibrotic processes in liver disorders, but the exact role of miR-202 is still unclear, and its related mechanisms are not fully understood.

Aims

The aim of this research is to analyze the regarded regulation of miR-202 on HGF and its role in the pathological progress of liver fibrosis.

Methods

In the present study, qRT-PCR was used to detect the expression level of miR-202 in serum of patients with liver fibrosis and to compare its expression in patients with different pathological stages. HGF was predicted to be the target gene of miR-202 by TargetScan and was verified by Dual-luciferase reporter gene assay. qRT-PCR and western blot were used to detect the regulatory effect of mir-202 on the mRNA and protein of HGF; effect of miR-202 on the expression of fibrosis factors α-smooth muscle actin (α-SMA), FSP1, and collagen was detected; effect of miR-202 on liver fibrosis in mice was detected by establishing CCL4-induced mouse model.

Results

We found that the expression level of miR-202 in serum of patients with liver fibrosis was significantly higher than that of healthy people, and increased with the increase of fibrosis; miR-202 inhibited the expression level of mRNA and protein of HGF by combining with the 3’-UTR of HGF; the expression level of miR-202 significantly increased after hepatic stellate cells (HSC) were stimulated by AngII; the overexpression of miR-202 could up-regulate the expression of fibrotic factors α-SMA, FSP1, and collagen I. In addition, miR-202 up-regulated the expression of collagen I and collagen III in liver tissue of mice with liver fibrosis and promoted the progress of liver fibrosis.

Conclusions

miR-202 could negatively regulate the expression of target gene HGF, activated HSC, and increased the expression levels of various fibrosis factors, and the pathological process of liver fibrosis injury was promoted.

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Funding

This work was supported by AIDS and viral hepatitis and other major infectious disease prevention and control, National Science and technology major projects, and sub topics new target research on anti HBV treatment (2012ZX10002006-003).

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Authors and Affiliations

  1. Key Laboratory of Viral Biology Guangzhou, Department of Biology, Jinan University, No.601, West Huangpu Avenue, Guangzhou, 510632, Guangdong, China

    Xianli Niu, Shirong Nong, Junyuan Gong, Xin Zhang, Hui Tang, Tianhong Zhou & Wei Li

  2. Department of Biochemistry and Molecular Biology, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong, China

    Xianli Niu

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  1. Xianli Niu
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Correspondence to Wei Li.

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Niu, X., Nong, S., Gong, J. et al. Research on promoting liver fibrosis injury by the targeted regulation of miR-202 for HGF to activate HSC. Ir J Med Sci 189, 1295–1304 (2020). https://doi.org/10.1007/s11845-020-02210-w

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  • DOI: https://doi.org/10.1007/s11845-020-02210-w

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