| Project/Area Number |
22591527
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
SAITO Takaharu 福島県立医科大学, 医学部, 博士研究員 (60508795)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Takuro 福島県立医科大学, 医学部, 医監兼教授 (20305361)
SATO Yoshihiro 福島県立医科大学, 医学部, 博士研究員 (60347218)
ANAZAWA Takayuki 福島県立医科大学, 医学部, 助教 (90566811)
ISE Kazuya 福島県立医科大学, 医学部, 講師 (90363746)
GOTOH Mitsukazu 福島県立医科大学, 医学部, 教授 (50162160)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 膵島移植 / High-mobility group box 1 / calreticulin / binding immunoglobulin protein / 細胞死 / DAMPｓ / HMGB-1 / マイトマイシンC |
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| Research Abstract |
Cellular stress or damage causes expression and release of endogenous molecules, such as damage-associated molecular patterns (DAMPs) molecules. High-mobility group box 1 (HMGB1) released from damaged islets has been shown to be associated with poor islet graft outcome, however, few studies evaluated implication of other endogenous molecules such as calreticulin as categorized DAMPs, and binding immunoglobulin protein (Bip) as categorized resolution-associated molecular patterns (RAMPs). Immediately after isolation, HMGB1, calreticulin as categorized DAMPs, and Bip, as categorized resolution-associated molecular patterns (RAMPs), signals were found in the cytoplasm of islet cells, more intensively as compared to those in islets in native pancreas. After culture for 1 day, only some of peripheral islet cells showed signals for these molecules, while central damaged areas, composed of necrotic cells but not apoptotic cells, strongly expressed these signals. Our findings suggest that necrotic process of the cells in central area after islet isolation and subsequent culture leads to express and release of not only DAMPs but also RAMPs, which might be responsible for counterbalance the DAMPs. A better understanding of the biological response to both DAMPs and RAMPs in isolated/cultured islets would improve its efficacy of islet transplantation.
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