| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
Emerging evidence suggests that the Rho/ROCK pathway is associated with pulmonary arterial hypertension (PAH). MURC/cavin-4, is a muscle-restricted caveolar-related protein. In this study, we found that in a chronic normobaric hypoxia model, MURC-knockout (MURC-/-) mice exhibited attenuated PAH and vascular remodeling compared with wild-type mice. Rat aortic smooth muscle cells had reduced RhoA activity, proliferation, and migration. Caveolin-1 (Cav1) which is a caveolar-related protein suppresses Rho/ROCK pathway through Gα13 inactivation. MURC bound to Cav1 and inhibited the association between Cav1 and the active form of Gα13, resulting in facilitated Rho activation. These results suggest that the association of MURC with Cav1 promotes Gα13-mediated Rho/ROCK activation, which causes vascular remodeling and subsequent PAH.
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