| Project/Area Number |
16K08232
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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 |
Biological pharmacy
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| Research Institution | Okayama University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
西堀 正洋 岡山大学, 医歯薬学総合研究科, 教授 (50135943)
高橋 英夫 近畿大学, 医学部, 教授 (60335627)
丹羽 淳子 近畿大学, 医学部, 講師 (60122082)
劉 克約 岡山大学, 医歯薬学総合研究科, 非常勤研究員 (40432637)
和氣 秀徳 岡山大学, 医歯薬学総合研究科, 講師 (60570520)
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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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 高ヒスチジン糖タンパク / HRG / 急性炎症 / 慢性炎症 / 敗血症 / 血漿タンパク / DAMPs / 肝 / 遺伝子発現 / 炎症 / 生活習慣病 |
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| Outline of Final Research Achievements |
Histidine-rich glycoprotein (HRG) is a plasma glycoprotein and secreted from liver. HRG has the multifunctional protective properties against the inflammatory progression, whereas little is known about the regulatory mechanisms of HRG production. In this study, we indicated that the gene expression of HRG was increased in both of spontaneously hypertensive (SHRSP rats) and streptozotocin-induced hyperglycemia (STZ rats) as chronic inflammatory models. The enhanced HRG expression in SHRSP rats was markedly reduced by sepsis-induced condition as acute inflammatory model. In addition, the sepsis condition-specific plasma proteins, which were recovered in HRG purification process from the sepsis-induced SHRSP rat plasma, were identified as HRG-associated protein. These proteins are known to be involved in inflammation pathology. These results suggest that HRG is regulated actively to protect against inflammatory impairments in various pathological conditions.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、急性炎症病態でみられる恒常性の破綻と障害が、慢性炎症病態ではHRGの中和抑制作用によって緩徐に進行するという病態仮説を提唱しており、炎症病態の学術的解明に対する新しい知見となる可能性がある。また、HRGは、敗血症のような急性炎症への補充療法に著効を示しており、新規バイオ医薬品として期待される。肝HRG遺伝子の発現制御機構や血漿HRGタンパクの動態を解析することは、HRG創薬開発のための前臨床研究として重要である。
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