2007 Fiscal Year Final Research Report Summary
Mechanosensory molecules and mechanical stress-induced primary responses in vascular endothelial cells.
| Project/Area Number |
18390075
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Kyushu University |
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Principal Investigator |
OIKE Masahiro Kyushu University, Faculty of Medicine, Associate Professor (70271103)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Hiroshi KYUSHU UNIVERSITY, Faculty of Dentistry, Assistant Professor (70304813)
HIRAKAWA Masakazu KYUSHU UNIVERSITY, Faculty of Medicine, Researcher (20380454)
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| Project Period (FY) |
2006 – 2007
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| Keywords | vascular endothelium / mechanical stress / integrin α5β1 / heparan sulfate proteoglycan / small molecule G protein / tyrosine kinases / actin stress fibers / TGFβ1 |
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| Research Abstract |
Vascular endothelial cells show their physiological functions in response to mechanical stresses. This project aimed to clarify the mechanosensory molecules and the mechanical stress-induced primary cellular responses in endothelial cells. We obtained the following results with cultured human umbilical cord vein endothelial cells and bovine aortic endothelial cells. Hypotonic stress induced the activation of small G protein RhoA and subsequently tyrosine phosphorylation of FAK and paxillin in endothelial cells. These primary responses then leaded to the release of ATP and transient reorganization of actin stress fibers. These hypotonic stress-induced signals and responses were completely inhibited by the pretreatment of the cells with anti-integrin α5β1 antibody and heparinase III, which cleaves the extracellular polysaccharide chain of heparan sulfate proteoglycan. In contrast, gene silencing of PECAM-1, which was previously reported as a part of mechanosensory molecules, with siRNA s
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howed no effects on hypotonic stress-induced transient reorganization of actin fibers. We have also observed that hypotonic stress-induced responses were completely abolished in TGFβ1-treated, mesenchymally transformed endothelial cells, thereby suggesting that endothelial morphology itself is a part of mechanosensory mechanisms. Another important finding of this project is that hypergravity as extracorporeal mechanical stress also induced the same intracellular signals and responses as hypotonic stress-induced responses in endothelial cells. These results indicate that there are at least two molecular structures that are involved in mechanosensation in vascular endothelial cells, i.e., the structure that consists of integrin α5β1 and heparan sulfate proteoglycan and that includes PECAM-1, and the former is probably sense gradual and sustained stresses including hypotonic stress and gravity change. We consider that the presence of multiple mechanosensory structures may be beneficial for using these molecules as therapeutic targets in the future. Less
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