miRNA-150-5p Promotes Hepatic Stellate Cell Proliferation and Sensitizes Hepatocyte Apoptosis During Liver Fibrosis

Abstract

Aim: To explore the role of miRNA-150-5p (miR-150-5p) in liver fibrosis. Materials & methods: miRNA expression profiles, CCl₄-induced liver fibrosis progression and regression rodent models, quantitative real-time PCR, miR-150-5p mimics and inhibitors, cell proliferation and apoptosis detection, RNA sequencing and bioinformatics analysis were employed. Results: Liver tissue miR-150-5p expression was positively associated with liver fibrosis progression and regression; however, miR-150-5p exhibited a cell-specific expression pattern, namely, it was enhanced in hepatocytes but reduced in hepatic stellate cells (HSCs) during liver fibrosis; miR-150-5p overexpression promoted HSC apoptosis and sensitized hepatocyte apoptosis; miR-150-5p mimic had a larger influence on the transcriptomic stability of HSCs than that of hepatocytes; miR-150-5p mediated activation of interferon signaling pathways might be responsible for HSC apoptosis. Conclusion: miR-150-5p exhibited an opposite regulation and function pattern between HSCs and hepatocytes during liver fibrosis.

Graphical abstract

miR-150-5p, not as identical as most of others, exhibited a cell-specific expression and function pattern: it was enhanced in hepatocytes but reduced in hepatic stellate cells (HSCs) during liver fibrosis; miR-150-5p overexpression promoted HSC apoptosis and sensitized hepatocyte apoptosis; miR-150-5p silence facilitated HSC proliferation and alleviated hepatocyte apoptosis under the pressure of proapoptotic factors. Taken together, miR-150-5p has potential effects on the pathogenesis of liver fibrosis, but cell-specific targeting carriers should be considered if miR-150-5p is chosen as a therapeutic target for liver fibrosis.

Keywords::

• apoptosis
• cell specific
• hepatic stellate cell
• hepatocyte
• liver fibrosis
• miR-150-5p
• proliferation
• transcriptome

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.comhttp://doi/suppl/10.2217/epi-2019-0104

Author contributions

H You and W Chen designed the study. W Chen wrote the manuscript. H You and W Chen revised the manuscript. W Chen, X Yan, A Yang, A Xu and T Huang performed the experiments and analyzed the data. All the authors read and approved the final manuscript.

Financial & competing interests disclosure

This work was supported by the National Natural Science Foundation of China (nos. 81800534, 81670539); the Seed Project from Beijing Friendship Hospital (no. YYZZ2017A07); the Natural Science Foundation of Capital Medical University (no. PYZ2017088); and the Rising Star Program from Beijing Friendship Hospital (no. yyqdkt2016-20). The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

Rodents-related studies were approved by the Animal Care and Use Committee of Beijing Friendship Hospital, Capital Medical University.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (nos. 81800534, 81670539); the Seed Project from Beijing Friendship Hospital (no. YYZZ2017A07); the Natural Science Foundation of Capital Medical University (no. PYZ2017088); and the Rising Star Program from Beijing Friendship Hospital (no. yyqdkt2016-20). The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties. No writing assistance was utilized in the production of this manuscript.