| Project/Area Number |
17K10526
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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 |
General surgery
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
萩原 信敏 日本医科大学, 医学部, 講師 (00328824)
松田 明久 日本医科大学, 医学部, 助教 (00366741)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 脂肪細胞 / 小胞体ストレス / アポトーシス / ミトコンドリア / PPAR-γ－アゴニスト / PPAR-γアゴニスト |
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| Outline of Final Research Achievements |
To elucidate the relationship between apoptosis induced by surgical stress and endoplasmic reticulum (ER) stress, we will examine (1) whether alpha-1 antitrypsin (A1AT) expression in adipocytes plays a role in regulating inflammation in adipocytes under endoplasmic reticulum stress and (2) whether rapamycin, which reduces endoplasmic reticulum stress, inhibits apoptosis induced by surgical stress. The survival rate after CLP in visceral obese mice was observed, and the relationship between (1) A1AT expression in adipose tissue and (2) the effect of rapamycin administration was analyzed. Inflammatory cytokines and CHOP expressions were measured in adipocytes lacking A1AT by siRNA transduction and ER stress induced by thapsigargin, and in adipocytes treated with thapsigargin followed by rapamycin. A1AT expression in adipocytes and reduction of ER stress by rapamycin prevented the overreaction of inflammation and improved the functional breakdown of adipose tissue.
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| Academic Significance and Societal Importance of the Research Achievements |
外科的侵襲によって誘導される細胞死に小胞体ストレスによるアポトーシスが関与していることが解明された．内臓脂肪細胞にA1ATが発現し，過剰な炎症性アディポカイン産生を抑制していること，さらにA1ATは小胞体ストレスストレス活性化に伴う脂肪組織の機能障害を防御していることが示された．またmTORシグナル経路の阻害が小胞体ストレスを伴うアディポカイン産生異常を抑制するのであれば，小胞体ストレスの軽減は脂肪組織の機能破綻や生存率を改善する可能性が考えられた．外科的侵襲と小胞体ストレスとの機構を考慮した手術侵襲後の合併症・臓器障害の病態解明は外科学にとって極めて重要であると考えられる．
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