2022 Fiscal Year Final Research Report
Elucidation of the vasoprotective mechanism of sepsis-associated DAMPs antagonist HRG
| Project/Area Number |
20K07290
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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 48030:Pharmacology-related
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| Research Institution | Kindai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
勅使川原 匡 岡山大学, 医学部, 客員研究員 (40403737)
王 登莉 岡山大学, 医歯薬学総合研究科, 助教 (40815693)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 高ヒスチジン糖タンパク質 / 敗血症 / 2価鉄イオン / 血管内皮細胞 / 細胞死 |
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| Outline of Final Research Achievements |
We have demonstrated that divalent iron ion-induced vascular endothelial cell damage, which is involved in the exacerbation of sepsis, is caused by the cell membrane peroxidation damage by mitochondria-derived reactive oxygen species generated as a result of mitochondrial damage due to endoplasmic reticulum stress response by divalent iron ion stimulation. In addition, plasma glycoprotein Histidine-rich glycoprotein (HRG) was found to exert cytoprotective effects by suppressing the endoplasmic reticulum stress response induced by divalent iron ion in vascular endothelial cell damage.
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| Free Research Field |
Pharmacology
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| Academic Significance and Societal Importance of the Research Achievements |
現在、有効な治療薬の存在しない敗血症病態において、HRGは非常に有望な治療薬候補となる。また、2価鉄イオンによる血管内皮細胞障害機序が明らかにされたことは、今後、重篤な組織・細胞傷害により誘発される細胞死反応をコントロールするための知見が得られたということであり、関連病態の治療薬・治療法開発の一助となる。
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