Blood-flow-mediated mechanotransduction in vascular endothelial cells
Project/Area Number |
22300150
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biomedical engineering/Biological material science
|
Research Institution | The University of Tokyo |
Principal Investigator |
YAMAMOTO Kimiko 東京大学, 大学院・医学系研究科, 講師 (00323618)
|
Co-Investigator(Kenkyū-buntansha) |
ANDO Joji 獨協大学, 医学部, 特任教授 (20159528)
|
Project Period (FY) |
2010 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2012: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2011: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
|
Keywords | バイオメカニクス / shear stress / 血管内皮細胞 / 細胞膜 / カベオラ / ATP / 流れ剪断応力 / イオンチャネル / カルシウム・シグナリング / プリノセプター |
Research Abstract |
Endothelial cells(ECs)sense shear stress and transduce blood flow infbrmation into functionalresponses that play important roles in vascular homeostasis and pathophysiology. A unique feature ofshear-stress-sensing is the involvement of many different types of membrane-bound molecules, but themechanisms remain unknown. Shear stress evokes a rapid, dose-dependent increase in intracellular Ca2+concentration caused by an influx of extracellular Ca2+via ATP-operated P2×4 ion channels activatedby endogenous ArP released by ECs. To analyze the dynamics of ArP release, we visualized ArP at thecell surface. When exposed to shear stress, ECs simultaneously released ArP at caveolae. Immediatelyafter the ArP release, Ca2+wave occurred at the same site as the ArP release. Caveolar membranefluidity increased over the entire EC membranes in response to shear stress. These findings indicate thatEC membranes directly respond to shear stress and that these changes link to shear-stress-mechanotranuction mechnisms.
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Report
(4 results)
Research Products
(74 results)