Analysis of liver regeneration through cell-cell interaction and identification of origin of regenerated hepatocytes

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07079
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: The University of Tokyo (2021); Institute of Physical and Chemical Research (2018-2020)
• Principal Investigator: Suzuki Toru 東京大学, 医科学研究所, 助教 (50334280)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 肝再生 / 細胞外膜小胞 / マイクロRNA

Outline of Final Research Achievements

Non-hepatic cells appear in liver parenchyma after chronic liver damages that are caused by abnormal mRNA turnover. We found that the appearance of non-hepatic cells was relevant to recovery from liver damage. Gene expression analyses showed that the non-hepatic cells displayed gene expression pattern similar to hepatocytes, suggesting that a conversion of non-hepatic cell to hepatocyte is responsible for liver regeneration. When we treated mice suffering chronic liver damage with a chemical inhibitor against release of extracellular vesicles (EVs), both the conversion from non-hepatic cell to hepatocyte and liver recovery were less efficient. By performing microRNA (miRNA) sequence, we found that several miRNA species are specifically enriched in blood plasma EVs from mice with chronic liver damage. These data suggest that miRNA-mediated regulation of gene expression contributes to liver regeneration through hepatic cell conversion in response to chronic liver damage.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

細胞外膜小胞は、様々な疾患に対する治療・検査診断への応用が進んでいる。現在では組織再生に及ぼす効果から、加齢に伴う皮膚の症状改善や美容効果、化粧品開発などでも導入が始まっている。肝疾患の治療においては、移植に必要な臓器の不足や、移植のみでは十分でない症例が存在することや移植後の組織を安定的に維持する必要性など、まだ改善すべき問題を抱えている。本研究から得られた成果は、障害を受けた肝臓に対してエクソソームを用いて機能回復、および正常な肝臓の維持効果を促す手法の開発につながると考えている。今後、効果の鍵となるマイクロRNAの特定と、誘導される分子機構の詳細な理解が必要となる。