The role of Reg family in pancreatitis
| Project/Area Number |
19K08405
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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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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
福井 広一 兵庫医科大学, 医学部, 准教授 (60378742)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | Reg / 急性膵炎 / 膵星細胞 / 慢性膵炎 / CRISPR/Cas9 / 腸内細菌叢 / 肝臓の脂肪化 / 細胞死 / 膵再生 / 遺伝子改変マウス |
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| Outline of Research at the Start |
Regenerating gene (Reg)は、損傷された膵臓が再生する過程で誘導される遺伝子としてクローニングされ、膵ラ氏島に対して細胞増殖作用を有し、膵再生関連因子として注目されている。また膵臓だけで無く、消化管粘膜の障害後の再生にもRegが関わっていることが知られている。本研究課題では、7遺伝子で構成されるReg familyのうち、6遺伝子を欠損させたマウスを作製、解析し、Regの本質的な生体内での役割解明を目指す。
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| Outline of Final Research Achievements |
Regenerating islet-derived (Reg) family proteins express in various mammalian tissues with multiple functions. They can also be induced after pancreas damage. To investigate the role of Reg in the pancreas following injury, we generated Reg1-3 deficient (Reg-/-) mice and examined them during cerulein-induced acute pancreatitis (AP) or cerulein and lipopolysaccharide-induced severe acute pancreatitis (SAP). Reg-/- mice showed no abnormalities in pancreas development and growth, did not affect the severity of pancreatitis or against pancreatic apoptosis in both AP and SAP model, and failed to stimulate pancreatic stellate cells (PSCs). We therefore conclude that Reg proteins might act to stimulate the PSCs contributing to pancreas repair.
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| Academic Significance and Societal Importance of the Research Achievements |
慢性膵炎は膵内の持続的な炎症により、膵外分泌細胞の脱落と線維化を特徴とする原因不明の慢性炎症性疾患である。膵外分泌、内分泌機能の低下による消化・吸収障害、糖尿病に加え、膵癌を高頻度に併発することから、原因の解明と治療法の開発が急がれている。その線維化の中心的な役割を果たすのが膵星細胞であり、同細胞をいかに制御するか、に注目が集まっている。
本研究課題ではその制御機構の一つとして、Reg遺伝子に注目し、解析を行ったものであり、Regを介した膵星細胞の活性化機構の解明が新たな治療標的となる可能性がある。
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Fusobacterium nucleatum confers chemoresistance by modulating autophagy in oesophageal squamous cell carcinoma.2020
Author(s)
Liu Y, Baba Y, Ishimoto T, Tsutsuki H, Zhang T, Nomoto D, Okadome K, Yamamura K, Harada K, Eto K, Hiyoshi Y, Iwatsuki M, Nagai Y, Iwagami S, Miyamoto Y, Yoshida N, Komohara Y, Ohmuraya M, Wang X, Ajani JA, Sawa T, Baba H.
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Journal Title
Br J Cancer.
Volume: 124
Issue: 5
Pages: 963-974
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Lung fibroblasts produce IL-33 in response to stimulation with retinoblastoma-binding protein 9 via production of prostaglandin E2.2020
Author(s)
Adachi T, Yasuda K, Muto T, Serada S, Yoshimoto T, Ishii KJ, Kuroda E, Araki K, Ohmuraya M, Naka T, Nakanishi K.
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Journal Title
Int Immunol.
Volume: 32
Issue: 10
Pages: 637-652
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Deletion in the cobalamin synthetase W domain-containing protein 1 gene is associated with congenital anomalies of the kidney and urinary tract.2020
Author(s)
Kanda S, Ohmuraya M, Akagawa H, Horita S, Yoshida Y, Kaneko N, Sugawara N, Ishizuka K, Miura K, Harita Y, Yamamoto T, Oka A, Araki K, Furukawa T, Hattori M.
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Journal Title
J Am Soc Nephrol
Volume: 31
Issue: 1
Pages: 139-147
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Necroptosis of intestinal epithelial cells induces type 3 innate lymphoid cell-dependent lethal ileitis.2019
Author(s)
Shindo R, Ohmuraya M, Komazawa-Sakon S, Miyake S, Deguchi Y, Yamazaki S, Nishina T, Yoshimoto T, Kakuta S, Koike M, Uchiyama Y, Konishi H, Kiyama H, Mikami T, Moriwaki K, Araki K, Nakano H.
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Journal Title
iScience
Volume: 15
Pages: 536-551
DOI
Related Report
Peer Reviewed / Open Access
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