| Project/Area Number |
16K08508
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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 physiology
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| Research Institution | Aichi Medical University |
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Principal Investigator |
Sato Motohiko 愛知医科大学, 医学部, 教授 (40292122)
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| Co-Investigator(Kenkyū-buntansha) |
林 寿来 愛知医科大学, 医学部, 講師 (30533715)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | シグナル伝達 / Ｇ蛋白質 / 血管新生 / 血管内皮増殖因子受容体 / 生理学 |
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| Outline of Final Research Achievements |
We previously identified activator of G-protein signaling 8 (AGS8) from a rat heart subjected to repetitive transient ischemia, which had substantial collateral developments. In this study, we examine a role of AGS8 on vascular formation. SiRNA-mediated AGS8 knockdown inhibited vascular endothelial growth factor (VEGF)-induced tube formation of human umbilical vein endothelial cell. AGS8-siRNA also attenuated VEGF-stimulated cell growth, migration and phosphorylation of VEGF receptor-2 (VEGFR-2) and downstream signaling molecules. Further analysis indicated that knockdown of AGS8 was associated with decrease of cell surface VEGFR-2 via regulating transport of VEGFR-2 to the plasma membrane. Moreover, knockdown of AGS8 suppressed angiogenesis of the mouse mesentery. These data suggest critical roles of AGS8 in vascular formation.
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| Academic Significance and Societal Importance of the Research Achievements |
血管内皮増殖因子は様々な疾病に伴う異常血管新生の標的とされている。血管内皮増殖因子は再生医療からも注目を浴びており、その細胞内シグナル制御を明らかにすることは非常に重要である。本研究によりAGS8が血管内皮増殖因子受容体の調節に関与することが明らかとなった。血管内皮増殖因子自体を標的とした抗体治療が行われているが、これらによる効果が不十分な時、または、副作用により使用できない時、AGS8が血管新生シグナルを制御する新しい治療標的となり得ると考えられた。
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