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Increased expression of caveolin‐1 is associated with upregulation of the RhoA/Rho kinase pathway and smooth muscle contraction in diabetes (1110.11)
Author(s) -
Mahavadi Sunila,
Nalli Ancy,
Kumar Divya,
Bhattacharya Sayak,
Zhou Ruizhe,
Grider John,
Murthy Karnam
Publication year - 2014
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.28.1_supplement.1110.11
Subject(s) - rhoa , rho associated protein kinase , downregulation and upregulation , caveolae , endocrinology , medicine , contraction (grammar) , caveolin 1 , protein kinase a , chemistry , kinase , signal transduction , microbiology and biotechnology , biology , biochemistry , gene
Gastrointestinal motility disorders are common among type I and type II diabetes and are shown to be associated with depletion of ICC and NOS‐containing neurons. Our recent studies in smooth muscle of diabetic mice and diabetic patients showed that hyperglycemia causes upregulation of RhoA/Rho kinase pathway leading to increase in sustained muscle contraction (tone). Caveolin‐1, an essential protein in the formation of caveolae, positively regulates RhoA/Rho kinase pathway in smooth muscle. Aim. To test the hypothesis that increase in caveolin‐1 expression causes upregulation of the RhoA/Rho kinase pathway in diabetes. Results. mRNA and protein expression of caveolin‐1 was increased in gastric smooth muscle from type 1 (NOD) and type 2 diabetic (db/db) mice and from diabetic patients. Treatment of muscle cells from control mice with 25 mM glucose for 48 h increased expression of caveolin‐1 and augmented ACh‐induced Rho kinase activity. The effect of high glucose on caveolin‐1 expression and Rho kinase activity was reversed by 72 h treatment in 5 mM glucose. Suppression of caveolin‐1 by siRNA attenuated the effect of high glucose on Rho kinase activity, whereas overexpression of caveolin‐1 in control cells augmented ACh‐induced Rho kinase activity. Conclusion. Increased expression of caveolin‐1 in smooth muscle contributes to upregulation of the RhoA/Rho kinase pathway and sustained contraction in diabetes. Grant Funding Source : DK28300 and DK15564