Mechanisms of hepatocyte proliferation mediated by exosomal miRNAs derived from adipose tissue

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16365
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Komiya Chikara 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (60825256)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: miRNA / エクソソーム / 脂肪組織 / 間葉系幹細胞 / NASH / Txnip

Outline of Final Research Achievements

Tamoxifen-inducible adipocyte-specific insulin receptor knockout (iFIRKO) mice are known to exhibit adipose tissue regeneration with increased numbers of adipose stem and progenitor cells (ASPCs). In this study, we identified miR-144-3p and miR-486a-3p as miRNAs that are commonly increased in serum exosome and the liver, and found that these miRNAs promote hepatocyte proliferation by suppressing Txnip expression as a target gene. While the expression levels of pri-miR-144-3p and pri-miR-486a-3p were not increased in the liver, they were elevated in adipose tissue, suggesting that these miRNAs may be delivered from adipose tissue to the liver via exosome during adipose tissue regeneration with increased ASPCs.

Free Research Field

内分泌代謝学

Academic Significance and Societal Importance of the Research Achievements

脂肪組織の再生過程で、肝細胞の増殖を促進するmiRNAが血中エクソソームで増加することを明らかにし、これらは脂肪組織で増加した間葉系前駆細胞群に由来する可能性が考えられた。間葉系幹細胞には傷害臓器の再生作用が報告されているが、本研究で同定されたmiR-144-3pとmiR-486a-3pは、残存する肝細胞を増殖させることで肝硬変に対する再生治療効果を有する可能性が考えられた。