2019 Fiscal Year Final Research Report

Functional analysis of sulfated glycans in ductular reactions

Research Project

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Project/Area Number	17K08758
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Experimental pathology
Research Institution	University of Fukui
Principal Investigator	Hoshino Hitomi 福井大学, 学術研究院医学系部門, 助教 (90500710)
Co-Investigator(Kenkyū-buntansha)	小林基弘福井大学, 学術研究院医学系部門, 教授 (00362137) 内村健治名古屋大学, 医学系研究科, 招へい教員 (20450835)
Project Period (FY)	2017-04-01 – 2020-03-31
Keywords	肝傷害 / 糖鎖
Outline of Final Research Achievements	The purpose of this study was to investigate the involvement of sulfated glycans in the development of ductular reactions. In this study, we prepared two types of liver injury model mice using mice deficient in the gene for sulfotransferase and analyzed the development of ductular reactions by immunohistochemical staining. Wild-type mice were fed DDC containing foods to prepare cholangiocytes injured model mice. We confirmed that ductular reactions were occured and the severity was increased in a time-dependent manner. Based on these preliminaly experiments, we prepared cholangiocytes injured model mice using mice deficient in the gene for sulfotransferase and examined whether the severity of ductular reactions were different comparing with wild-type mice. There was no significant difference between wild-type mice and mice deficient in the gene for sulfotransferase.
Free Research Field	糖鎖生物学
Academic Significance and Societal Importance of the Research Achievements	劇症肝炎をはじめとする種々の肝疾患では、門脈域周辺に細胆管反応がみられるが、その発生メカニズムや病理学的意義は十分には明らかになっていない。本研究では硫酸化糖鎖に着目して、細胆管反応の発生メカニズム解明を試みたが、モデルマウスを用いた実験で、硫酸化糖鎖が細胆管反応の発生メカニズムに関与することを明らかにできなかった。近年、ヒトで生じる肝傷害とモデルマウスで生じる肝傷害では病態形成に関与する分子が異なっていることが報告されており、モデルマウスの作製方法についても議論がなされている。細胆管反応の病理学的意義を明らかにすることは、慢性肝疾患、さらには癌の治療や予防に貢献すると考えられる。