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Contraction of myofibroblasts in granulation tissue is dependent on Rho/Rho kinase/myosin light chain phosphatase activity
Author(s) -
Tomasek James J.,
Vaughan Melville B.,
Kropp Bradley P.,
Gabbiani Giulio,
Martin Michael D.,
Haaksma Carol J.,
Hinz Boris
Publication year - 2006
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1743-6109.2006.00126.x
Subject(s) - myosin light chain kinase , rho associated protein kinase , myofibroblast , myosin light chain phosphatase , contraction (grammar) , myosin , chemistry , granulation tissue , microbiology and biotechnology , phosphatase , kinase , wound healing , phosphorylation , medicine , biology , endocrinology , biochemistry , immunology , fibrosis
During wound healing and fibrocontractive diseases fibroblasts acquire a smooth muscle cell‐like phenotype by differentiating into contractile force generating myofibroblasts. We examined whether regulation of myofibroblast contraction in granulation tissue is dominated by Ca 2+ ‐induced phosphorylation of myosin light chain kinase or by Rho/Rho kinase (ROCK)‐mediated inhibition of myosin light chain phosphatase, similar to that of cultured myofibroblasts. Strips of granulation tissue obtained from rat granuloma pouches were stimulated with endothelin‐1 (ET‐1), serotonin, and angiotensin‐II and isometric force generation was measured. We here investigated ET‐1 in depth, because it was the only agonist that produced a long‐lasting and strong response. The ROCK inhibitor Y27632 completely inhibited ET‐1–promoted contraction and the phosphatase inhibitor calyculin elicited contraction in the absence of any other agonists, suggesting that activation of the Rho/ROCK/myosn light chain phosphatase pathway is critical in regulating in vivo myofibroblast contraction. Membrane depolarization with K + also stimulated a long‐lasting contraction of granulation tissue; however, the amount of force generated was significantly less compared to ET‐1. Moreover, K + ‐induced contraction was inhibited by Y27632. These results are consistent with inhibition of myosin light chain phosphatase by the Rho/ROCK signaling pathway, which would account for the long‐duration contraction of myofibroblasts necessary for wound closure.