Underlying mechanisms and therapeutic implications of a novel accelerator of fibrotic liver regeneration

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15974
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Tokai University
• Principal Investigator: YANAGAWA Takayo 東海大学, 医学部, 助教 (10760291)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 肝再生 / 線維肝 / 再生医療 / エクソソーム

Outline of Final Research Achievements

We previously identified opioid growth factor receptor like-1 (OGFRL1) as a novel accelerator of fibrotic liver regeneration in mice. In the present study, we have implicated OGFRL1 in regeneration of the injury/fibrotic liver. Among the peripheral blood cells, monocytes were the major source of OGFRL1. Liver tissue contained a small but significant amount of Ogfrl1 mRNA, which was decreased following repeated CCl4 injections. OGFRL1 was transiently detected in the serum as an exosome-included protein and localized in hepatocytes surrounding the necrotic areas after CCl4-induced liver injury/fibrosis. Administration of OGFRL1-expressing cells into mice with liver fibrosis enhances mobilization of hepatic progenitor cells and stimulates proliferation of hepatocytes after partial hepatectomy.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

内在性OGFRL1の挙動をはじめとして、OGFRL1による線維化改善と再生促進機序の分子機構の一端を明らかにすることが出来た。肝硬変に対する新規の治療法としては、国内外において細胞移植が試みられているが、細胞の品質管理や移植後の造腫瘍性といった問題点も存在する。今後、線維肝におけるOGFRL1の再生促進機序をより詳細に解明することで、OGFRL1またはその下流因子を発現させて高機能化した少数の自家細胞を移植する方法やエクソソーム内包タンパク質として投与するなど、難治性肝硬変症例に対する新たな再生治療の開発が期待できる。