Regulatory mechanisms of focal cell death during liver regeneration in severe fatty liver

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09192
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kanazawa University
• Principal Investigator: INABA YUKA 金沢大学, 新学術創成研究機構, 准教授 (20571970)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 非アルコール性脂肪性肝疾患 / 細胞ストレス / 肝再生 / 肝細胞死 / FRET

Outline of Final Research Achievements

The liver has robust regenerative potential in response to damage, but this potential is impaired in hepatic steatosis. In particular, impaired liver regeneration in severe fatty liver is a trigger for complications after hepatectomy. We have found that solitary cell death and focal cell death (necrosis) occur in regenerating severe fatty liver after hepatectomy, and that this focal cell death is an important trigger for impaired fatty liver regeneration. In this study, we found that the stress response gene activating transcription factor 3 (ATF3) is important for regulation of focal cell death during liver regeneration in severe fatty liver.

Free Research Field

肝臓学、代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究の核心は、「高度脂肪肝において、肝切除術後合併症の誘因となる再生障害が、どのようなメカニズムにより発症するのか？」という学術的問いである。肝切除後合併症の発症に関与する広汎細胞死の誘導メカニズムは、現在までに明らかにされていない。本研究成果は、広汎細胞死の制御メカニズムを明らかにしたものであり、高度脂肪肝における術後合併症の病態・病因の理解とともに、新規な治療法の開発に繋がる。