1998 Fiscal Year Final Research Report Summary
Molecular Mechanisms for Mechanotransduction in Vascular Smooth Muscle and Endothelial cell
| Project/Area Number |
09470007
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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 physiology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TAKUWA Noriko The University of Tokyo Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (70150290)
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| Co-Investigator(Kenkyū-buntansha) |
TAKUWA Yoh Kanazawa University School of Medicine, Professor, 医学部・生理学第一講座, 教授 (60171592)
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| Project Period (FY) |
1997 – 1998
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| Keywords | vascular / smooth muscle / mechanical stretch / ATP / P_0 purinoceptor / signal transduction / gene expression / JNK |
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| Research Abstract |
Mechanical strain has been implicated in phenotypic changes, including alteration of gene expression in vascular smooth muscle cells ; however, the molecular basis for mechanotransduction leading to nuclear gene expression is largely unknown. By using a FLEXERCELL^R strain unit, we found that cyclic stretching of vascular smooth muscle cells dramatically activates Jun N-terminal kinase(JNK)/stress-activated protein kinase(SAPK)through an autocrine mechanism. Stretch causes time-and strength-dependent rise of the ATP concentration in media. The stretch-induced activation of JNK/SAPK is attenuated by the addition of hexokinase or apyrase that scavenge ATP in media. Both the P_2 receptor antagonist and the A_1 subtype-selective P_1 receptor antagonist partially inhibit stretch-induced activation of JNK/SAPK.The conditioned medium from stretched cells contains an activity to stimulate JNK/SAPK.The JNK-stimulating activity in the conditioned medium from stretched cells is attenuated by the addition of apyrase or P_1 and P_2 receptor antagonists. The addition of exogenous ATP or adenosine induces dose-dependent activation of JNK/SAPK.These results indicate that stretch activates JNK/SAPK in vascular smooth muscle cells through mechanisms involving autocrine stimulation of purinoceptors by ATP and its hydrolyzed product adenosine.
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Research Products
(20 results)
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[Publications] M.Hirakata, S.Kaname, U.Chung, N.Joki, Y.Hori, M.Noda, Y.Takuwa, T.Okazaki, T.Fujita, T.Katoh, and K.Kurokawa.: "Tyrosine kinase dependent expression of TGF-beta induced by stretch in mesangial cells." Kid.International. 51. 1028-1036 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Y.Takuwa, K.Hamada, J.Abe, K.Chang, J.Deguchi and N.Takuwa.: "Functional roles of locally produced vasoactive substances in vascular reponses to mechanical stress and injury." CVD Grand Round Series Vol.3 (Ed.T.Asano, T.Hayakawa, T.Kirino, T.Ohta, K.Sano, T.Sasaki, K.Takakura and A.Tamura, Tokyo) Neuron Publishing Co., Ltd.Tokyo Vol 4 : 93-105,1997.
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[Publications] H.Okamoto, N.Takuwa, K.Gonda, H.Okazaki, K.Chang, Y.Yatomi, H.Shigematsu, and Y.Takuwa.: "EDG1 is a functional sphingosine-1-phosphate receptor that is linked via a G_<i/o> to multiple signaling pathways, including phospholipase C activation, Ca^<2+> mobilization, ras-mitogen-activated protein kinase activation, and adenylate cyclase inhibition." J.Biol.Chem.273. 27104-27110 (1998)
Description
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