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Exosome-associated miRNA-99a-5p targeting BMPR2 promotes hepatocyte apoptosis during the process of hepatic fibrosis

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Abstract

Liver fibrosis is a serious stage of chronic liver injury. Inhibition of hepatic stellate cells activation and hepatocytes apoptosis is important measures in the treatment of liver fibrosis. Studies have shown that exosomes are involved in regulating the information transmission between cells, but there are few studies on the interaction between exosomes from HSC and hepatocytes. This study screened miRNAs with significant differences related to liver fibrosis in the database. Then, we activated HSC applying transforming growth factor β1 (TGF-β1) and collected exosomes. The expression of miRNA in HSC-derived exosomes was verified by quantitative real-time PCR (qRT-PCR). The results of cell function test showed that HSC-derived exocrine miRNA-99a-5p could inhibit hepatocytes proliferation and promote hepatocytes apoptosis. Conversely, inhibition of miRNA-99a-5p can promote hepatocytes proliferation and inhibit apoptosis. Target gene prediction and luciferase assay show that miRNA can specifically bind to BMPR2 site sequence. In addition, we also detected the expression of BMPR2 and apoptosis-related protein by qRT-PCR and Western blot (WB). In conclusion, this study demonstrates that HSC-derived exocrine miRNA-99a-5p can promote hepatocytes apoptosis and participate in the process of liver fibrosis by targeting BMPR2. Our findings highlight the therapeutic potential of HSC-derived exocrine miRNA-99a-5p in hepatic fibrosis.

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The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.

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Acknowledgements

We are grateful to the Science and Technology Project of Hainan Province & Hainan Province Clinical Medical Center. Finally, we thank the reviewers.

Funding

The study was funded by the Science and Technology Project of Hainan Province, Hainan Natural Science Foundation, Grant/Award Number: Nos. 821QN0983 and 819QN387, the healthy department of Hainan province (20A200104). This research was also supported by Hainan Province Clinical Medical Center.

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Authors and Affiliations

  1. Department of Clinical Laboratory, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, 570311, Hainan, China

    Feng Li

  2. Baoding First Central Hospital, Baoding, 071000, Heibei, China

    Tengfei Yan

  3. Central Laboratory, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, 570208, Hainan, China

    Shunlan Wang & Xiaohong Wen

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  1. Feng Li
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Contributions

FL designed and conceived, performed the experiments, analysed the data, and approved the final draft. XH W prepared figures and/or tables, and approved the final draft. TF Y, SL W performed some of the experiments. All the authors have reviewed and approved the final version of the manuscript.

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Correspondence to Feng Li or Xiaohong Wen.

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Li, F., Yan, T., Wang, S. et al. Exosome-associated miRNA-99a-5p targeting BMPR2 promotes hepatocyte apoptosis during the process of hepatic fibrosis. Clin Exp Med 23, 4021–4031 (2023). https://doi.org/10.1007/s10238-023-01122-0

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