Abstract:
:Emerging evidence suggests that caveolin-1 (Cav1) is associated with pulmonary arterial hypertension. MURC (also called Cavin-4) is a member of the cavin family, which regulates caveolar formation and functions together with caveolins. Here, we show that hypoxia increased Murc mRNA expression in the mouse lung, and that Murc-null mice exhibited attenuation of hypoxia-induced pulmonary hypertension (PH) accompanied by reduced ROCK activity in the lung. Conditional knockout mice lacking Murc in smooth muscle also resist hypoxia-induced PH. MURC regulates the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) through Rho/ROCK signalling. Cav1 suppresses RhoA activity in PASMCs, which is reversed by MURC. MURC binds to Cav1 and inhibits the association of Cav1 with the active form of Gα13, resulting in the facilitated association of the active form of Gα13 with p115RhoGEF. These results reveal that MURC has a function in the development of PH through modulating Rho/ROCK signalling.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Nakanishi N,Ogata T,Naito D,Miyagawa K,Taniguchi T,Hamaoka T,Maruyama N,Kasahara T,Nishi M,Matoba S,Ueyama Tdoi
10.1038/ncomms12417subject
Has Abstractpub_date
2016-08-22 00:00:00pages
12417issn
2041-1723pii
ncomms12417journal_volume
7pub_type
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