| Project/Area Number |
16K09401
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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 |
Gastroenterology
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 急性膵炎 / S100g / カルシウム / トリプシン / 細胞内カルシウム / ANXA10 / アミラーゼ分泌 / Anxa10 |
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| Outline of Final Research Achievements |
S100g is a calcium-binding protein, which is mainly expressed in the duodenum. The expression of S100g in the pancreas was induced in experimental pancreatitis and pancreatic injury was decreased in S100g knock-out (KO) mice. We produced AR42J-S100g cells, which over-expressed S100g in a pancreatic exocrine model; AR42J cells. In these cells, amylase secretion in response to cholecystokinin (CCK-8) was inhibited and the increase of intracellular calcium concentration ([Ca2+]i) was restricted. Therefore, S100g was suspected to be a risk factor of pancreatitis. In the experimental pancreatitis of S100g KO mice, it seems that the increase of [Ca2+]i in response to CCK-8 was not restricted, the secretion from pancreatic acinar cells stayed in the high level, and the amount of intracellular trypsinogen decreased compared to the control mice, resulting in the reduction of pancreatic injury with the decrease of ectopic activation of trypsinogen.
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| Academic Significance and Societal Importance of the Research Achievements |
急性膵炎は膵内でのトリプシンの異所性活性化が原因と考えられてきたが、多くの研究結果から、それ以外にも、NF-kBの活性化、オートファジー不全、小胞体ストレス、酸化ストレス、カルシウムシグナル異常などの多くの異常が並行して起こっていることが明らかになってきた。しかし、詳細なメカニズムは未だに不明である。急性膵炎が発症すると外分泌不全が生ずるが、本研究はそれにS100gが関与している可能性があること、S100gを抑制し外分泌を維持することで、膵傷害を軽減できる可能性があることを示したものである。もちろん細胞内カルシウムシグナルは他の因子でも調節されており、さらなる検討が必要である。
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