The Role of Amniotic Epithelial Cell-derived miRNAs in the Regulation of Hepatic Stellate Cell Activation

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23732
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0701:Biology at molecular to cellular levels, and related fields
• Research Institution: Nihon University
• Principal Investigator: MIKI Toshio 日本大学, 医学部, 教授 (80845305)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 羊膜上皮細胞 / 肝線維化 / エクソソーム / マイクロRNA / 肝星細胞 / プロテオミックス

Outline of Final Research Achievements

The study aimed to elucidate the antifibrotic mechanism of the amniotic epithelial cell (AEC)-derived exosomal micro RNA (miRNA). It has been shown that AEC condition media possess an anti-fibrotic effect using rodent models. In the effort to find the potent factors, we found the AEC-derived exosome contained miRNA plays a key role. Using exosome RNA sequencing, we identified one uniquely expressed exosomal miR, miR-483-5p. In this study, we performed quantitative proteomic analysis, which revealed miR-483-5p affected signaling pathway in spontaneously activating human primary HSCs. The involvement of the identified protein was validated with the hAEC-derived exosome-treated HSC cell line cells. In conclusion, our findings elucidated the contribution of hAEC exosomal miR483-5p represents a previously undescribed and unique anti-fibrotic mechanism via suppressing PDLIM3 and other actin-related molecule expressions.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

肝線維化の進行過程においては、肝細胞傷害に起因する炎症反応によって肝星細胞が筋線維芽細胞様に活性化する過程が最も重要な要因であるとされる。そこでわれわれは肝星細胞活性化を抑制する一つの手段として、羊膜上皮細胞由来エクソソームによって伝達されるマイクロRNAに注目し、その肝線維化抑制作用を解明した。これらの成果から、肝硬変の新規治療法として、羊膜上皮細胞由来エクソソームの応用や、今回同定した細胞内シグナル経路をターゲットとした治療薬の開発が期待される。