Establishment of novel target molecules for pancreatic diseases by regulating stellate cell activation
| Project/Area Number |
17K10713
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Showa University |
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Principal Investigator |
LEI XIAOFENG 昭和大学, 医学部, 普通研究生 (00595069)
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| Co-Investigator(Kenkyū-buntansha) |
金山 朱里 昭和大学, 医学部, 准教授 (10338535)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 膵臓線維化 / 膵臓星細胞 / Hic-5 / 膵炎 / 慢性膵炎 / 膵癌 / 膵星細胞 / 膵疾患 |
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| 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.
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| 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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Report
(4 results)
Research Products
(6 results)
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[Journal Article] Light-at-night exposure affects brain development through pineal allopregnanolone-dependent mechanisms2019
Author(s)
Haraguchi S, Kamata M, Tokita T, Tashiro KI, Sato M, Nozaki M, Okamoto-Katsuyama M, Shimizu I, Han G, Chowdhury VS, Lei XF, Miyazaki T, Kim-Kaneyama JR, Nakamachi T, Matsuda K, Ohtaki H, Tokumoto T, Tachibana T, Miyazaki A, Tsutsui K.
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The impact of stromal Hic-5 on the tumorigenesis of colorectal cancer through lysyl oxidase induction and stromal remodeling.2018
Author(s)
Omoto T, Kim-Kaneyama JR, Lei XF, Orimo A, Ohnishi K, Yoshihara K, Miyauchi A, Li S, Gao L, Umemoto T, Tanaka J, Nakahara K, Takeya M, Ishida F, Kudo SE, Haraguchi S, Miyazaki T, Miyazaki A.
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Journal Title
Oncogene.
Volume: 37
Issue: 9
Pages: 1205-1219
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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