2021 Fiscal Year Final Research Report

Interaction between hepatocytes and stellate cells in NASH

Research Project

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Project/Area Number	19K07509
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	Nagoya City University
Principal Investigator	Naiki-Ito Aya 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (20509236)
Co-Investigator(Kenkyū-buntansha)	野尻俊輔名古屋市立大学, 医薬学総合研究院(医学), 教授 (50381843) 高橋智名古屋市立大学, 医薬学総合研究院(医学), 教授 (60254281) 加藤寛之名古屋市立大学, 医薬学総合研究院(医学), 講師 (80791293)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	細胞間コミュニケーション / 疾患モデル / 肝線維化
Outline of Final Research Achievements	Transgenic rats with dominant negative mutant of connexin 32, a hepatocyte gap junction protein, and dysfunction of gap-junctional intercellular communication, were treated with a high fat diet and dimethylnitrosamine to establish a model for induction of NASH, fibrosis, as well as insulin resistance. TNFα, Tgfβ1, NF-κB and JNK signaling was involved in the activation of hepatic stellate cells and NASH progression. Intake of chemicals inhibiting those signaling was found to have an inhibitory effect on NASH and fibrosis.
Free Research Field	実験病理学
Academic Significance and Societal Importance of the Research Achievements	本研究では、ヒトのNASHで頻繁に併発するメタボリックシンドロームや肝線維症を随伴するNASHモデルを樹立した。このモデルを用いて、NASHに対する効果とそのメカニズムの検証が可能であることが明らかとなり、NASHの化学予防研究に有用なツールとなりえる。