Elucidation of HCC carcinogenic mechanism from the viewpoint of liver fibrosis and development of new treatment methods

Research Project

Project/Area Number	16K09365
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Gastroenterology
Research Institution	Nagoya City University
Principal Investigator	NOJIRI SHUNSUKE 名古屋市立大学, 医薬学総合研究院(医学), 教授 (50381843)
Co-Investigator(Kenkyū-buntansha)	三浦裕至学館大学, 健康科学部, 教授 (90285198)
Project Period (FY)	2016-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000) Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	ATBF1 / 肝臓線維化 / 肝線維化 / 肝硬変 / ＡＴＢＦ１ / 内科
Outline of Final Research Achievements	We confermed the expression of ATBF1 and many genes that was concerned liver fibrosis such as collagen I, PDGFR, HNF1, AFP, TGFβ,TNFα,PPARα,PPARγ. The change of each gene was observed by forced expression and knockdown of ATBF1. Significant increased expression of collagen I and PDGFR was observed by ATBF1 expression. These changes was observed by X-ray irradiation and these reactions weakened under ATBF1 expression suppression. ATBF1 knockout mouse is beeng created, and will be tested in vivo as soon as it is completed.
Academic Significance and Societal Importance of the Research Achievements	肝臓病の終末病態である肝硬変は肝臓の星細胞の活性化によって起こる慢性の線維化が原因の一つとされている。これらは様々な肝臓にかかるストレスによって起こるがそのシグナル経路の一つがATBF1を介したcollagen Iの活性化によって起こることが細胞レベルで明らかになった。今後は動物実験で確かめることが必要であり今後この経路に着目した肝硬変の治療薬の開発につながる可能性があると考えている。