Rho A and the Rho kinase pathway regulate fibroblast contraction: Enhanced contraction in constitutively active Rho A fibroblast cells |
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Authors: | Koji Nobe Hiromi Nobe Hiroko Yoshida Richard J. Paul |
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Affiliation: | a Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan b Dermatology Division, Department of Medicine, UCLA, Los Angeles, CA, USA c Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA d Department of Physical Therapy, Bunkyo-Gakuin University, Japan |
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Abstract: | Fibroblast cells play a central role in the proliferation phase of wound healing processes, contributing to force development. The intracellular signaling pathways regulating this non-muscle contraction are only partially understood. To study the relations between Rho A and contractile responses, constitutively active Rho A (CA-Rho A) fibroblast cells were reconstituted into fibers and the effects of calf serum (CS) on isometric force were studied. CS-induced force in CA-Rho A fibroblast fibers was twice as large as that in wild type (NIH 3T3) fibroblast fibers. During this response, the translocation of Rho A from the cytosol to the membrane was detected by Rho A activity assays and Western blot analysis. Pre-treatment with a Rho specific inhibitor (C3-exoenzyme) suppressed translocation as well as contraction. These results indicate that Rho A activation is essential for fibroblast contraction. The Rho kinase inhibitor (Y27632) inhibited both NIH 3T3 and CA-Rho A fibroblast fiber contractions. Activation of Rho A is thus directly coupled with Rho kinase activity. We conclude that the translocation of Rho A from the cytosol to the membrane and the Rho kinase pathway can regulate wound healing processes mediated by fibroblast contraction. |
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Keywords: | Wound healing Fibroblast Contraction Rho A Rho kinase Collagen |
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