Analysis of the effects by the regulation of integrative stress response to impaired liver regeneration in NAFLD

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H05678
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Kanazawa University
• Principal Investigator: Inaba Yuka 金沢大学, 新学術創成研究機構, 助教 (20571970)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 非アルコール性脂肪性肝疾患 / 肝切除 / 肝再生 / 統合的ストレス応答 / 細胞死

Outline of Final Research Achievements

The liver has robust regenerative potential in response to damage, but hepatic steatosis weakens this potential. That is known the impaired liver regeneration causes complications after surgery, such as liver failure. However the detail of mechanisms was unclear. The enhanced integrated stress response (ISR) is commonly induced by various cellular stress. We found that ISR plays a key role in impaired regeneration of hepatic steatosis. In this study, we revealed that stress induced transcription factor has an important role as the mechanism of liver regeneration disorder in fatty liver disease.

Free Research Field

肝臓学・代謝学

Academic Significance and Societal Importance of the Research Achievements

代表者は、脂肪肝における重篤な再生障害を引き起す誘因として、壊死を伴う細胞死が重要であること、その細胞死の誘導にストレス誘導性転写因子ATF3が重要な役割を担うことを明らかにした。本研究成果は、脂肪肝再生障害における細胞死誘導の新規メカニズムの解明という学術的意義を有する。また、再生障害の重症化の病態理解と新規治療標的に関する新たな知見という社会的意義を有する。