2021 Fiscal Year Final Research Report
A role of Activator of G-protein signaling 8 in pulmonary hypertension
Project/Area Number |
19K07309
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 48020:Physiology-related
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Research Institution | Aichi Medical University |
Principal Investigator |
Sato Motohiko 愛知医科大学, 医学部, 教授 (40292122)
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Co-Investigator(Kenkyū-buntansha) |
山村 彩 愛知医科大学, 医学部, 講師 (40633219)
林 寿来 愛知医科大学, 医学部, 講師 (30533715)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | 細胞内情報伝達 / G蛋白質 / AGS8 |
Outline of Final Research Achievements |
Activator of G-protein signaling 8 (AGS8, also known as fibronectin type III domain containing 1: FNDC1) was isolated from a rat heart subjected to repetitive transient ischemia in screen of signaling molecules, which influenced G-protein mediated signaling pathway. AGS8 regulated vascular endothelial growth factor receptor signaling and was involved in the development of vessels. In this study, we examined a potential of AGS8 on signal formation by other growth factor receptors including platelet-derived growth factor (PDGF) receptor. AGS8 knockdown by siRNA reduced PDGF-mediated signaling in endothelial cells and smooth muscle cells. AGS8 inhibitor showed possible reduction of pulmonary hypertension in which model PDGF played an important role. The observations suggested an involvement of AGS8 in PDGF signal and a potential of AGS8 as a therapeutic target of human diseases.
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Free Research Field |
生理学
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Academic Significance and Societal Importance of the Research Achievements |
いくつかの癌種でAGS8が高発現していることが報告され、また、他の病態においてもAGS8の関与が指摘されている。本研究により、AGS8がPDGF受容体シグナルを制御する可能性、また、AGS8阻害薬が個体内で機能する可能性が示された。AGS8阻害薬は、腹腔内投与および皮下投与で生体投与への一定の許容性を示し、治療効果が期待できる結果が得られた意義は大きいと考える。本研究の結果はAGS8を標的とした治療の可能性を示すものとして意義があると考えられた。
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