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Caveolin‐1‐Dependent Regulation of Myocardin Expression and Contractile Phenotype in Colonic Circular Smooth Muscle
Author(s) -
Bhattacharya Sayak,
Kendig Derek,
Grider John,
Murthy Karnam
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1002.14
Subject(s) - myocardin , microbiology and biotechnology , myosin , caveolae , biology , rho associated protein kinase , calponin , actin , chemistry , endocrinology , signal transduction , medicine , serum response factor , transcription factor , biochemistry , gene
The signaling molecules in smooth muscle are compartmentalized by binding to caveolin‐1, a key protein in the formation of caveolae. Our recent studies showed that carbachol‐induced Rho kinase activity and colonic smooth muscle contraction, and colonic propulsion were decreased in caveolin‐1 knockout (Cav‐1 ‐/‐ ) mice. The aim of this study is to test the hypothesis that caveolin‐1 acts as a pro‐contractile and anti‐proliferative regulatory molecule that promotes smooth muscle function. Expression of myocardin, a co‐activator of the transcription factor serum response factor, and microRNA‐144 that regulate smooth muscle phenotype was decreased in colonic circular smooth muscle of Cav‐1 ‐/‐ mice, and by silencing caveolin‐1 expression in control cultured muscle cells. Decrease in myocardin in Cav‐1 ‐/‐ mice was accompanied by a decrease in smooth muscle myosin heavy chain (SM‐MHC) expression and increase in EGF receptor phosphorylation and ERK1/2 activity. Treatment of muscle cells with carbachol for 24 h increased myocardin expression; the increase in expression was blocked by inhibitors of Rho kinase (Y27632) and actin polymerization (cytochalasin D), implying that changes in expression of myocardin in Cav‐1 ‐/‐ mice could be a consequence of the decrease in Rho kinase activity in these mice. We conclude that caveolin‐1 promotes myocardin expression and contractile phenotype via a Rho/Rho kinase pathway.