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2019 Fiscal Year Final Research Report

Establishment of novel target molecules for pancreatic diseases by regulating stellate cell activation

Research Project

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Project/Area Number 17K10713
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionShowa University

Principal Investigator

LEI XIAOFENG  昭和大学, 医学部, 普通研究生 (00595069)

Co-Investigator(Kenkyū-buntansha) 金山 朱里  昭和大学, 医学部, 准教授 (10338535)
Project Period (FY) 2017-04-01 – 2020-03-31
Keywords膵臓線維化 / 膵臓星細胞 / Hic-5
Outline of Final Research Achievements

We aimed to investigate whether Hic-5 activates pancreatic stellate cells (PSCs) and thereby promotes development of pancreatic fibrosis in chronic pancreatitis (CP).We used immunofluorescence and immunohistochemistry to analyze expression levels of Hic-5 in human and mouse pancreatic tissue. Hic-5 expression was strongly upregulated in activated PSCs cultured from human pancreatic tissue and mouse pancreatic fibrosis taken from wild-type mice with cerulein-induced CP. In Hic-5 knockout mice, pancreatic fibrosis and PSC activation were significantly attenuated. In the activated PSCs of Hic-5 knockout mice, the TGF-β/Smad2 signaling pathway was significantly inhibited, resulting in reduced collagen production and reduced α-smooth muscle actin expression. Together, these results show that Hic-5 is a potential marker of activated PSCs and therapeutic target for the treatment of CP.

Free Research Field

膵臓

Academic Significance and Societal Importance of the Research Achievements

本研究では膵実質細胞そのものを治療標的としている現在の治療概念と異なり、間質に存在する星細胞に着目する点に特色がある。またPSCの組織線維化や治療抵抗性への寄与からもその重要性は明らかである。また疾患の発症機構を細胞外環境応答因子という側面から解析する点は学術的意義が多いと思う。これまでに、心血管領域の疾患を中心に解析を行ってきたが、さらにHic-5が様々な他の疾患発症に関与する。また将来的な創薬ターゲットとして、癌、線維症、血管疾患などの生活習慣に起因する複数の疾患を同時に標的にできる治療ターゲット分子となる可能性を含むことから革新性が期待される。その発見が社会的の意義やインパクトは大きい。

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Published: 2021-02-19  

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