The effect of local Rho-kinase inhibition on murine wound healing

Sunil S. Tholpady, Brent R. Degeorge, Chris A. Campbell

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

INTRODUCTION: The process of cutaneous wound healing and contraction is a complex orchestra of temporally and spatially controlled signaling moieties and pathways. Rho-kinase (ROCK) has been implicated as a key downstream effector of transforming growth factor β1 (TGF-β1) signal transduction, which ultimately coordinates α-smooth muscle actin (α-SMA)-mediated wound contraction. Previous in vitro studies of ROCK inhibition have demonstrated decreased fibroblast contraction and epithelial advancement after wounding. In vivo systemic ROCK inhibition revealed modest late wound healing attenuation in contrast to α-SMA knock-out rodents. The goal of this investigation was to explore the effect of local delivery of a ROCK inhibitor on an in vivo murine model of wound healing. METHODS: Full-thickness cutaneous wounds were created in 24 white mice and were treated daily with local topical delivery of 100 μL of 10 M ROCK inhibitor (Y27632) or saline control. Percent wound surface area over time and compensatory epithelial advancement was quantified. After 12 days, tissue was harvested for assessment of inflammatory cellular density, immunohistochemistry for α-SMA, and TGF-β protein expression. RESULTS: Wounds subjected to local ROCK inhibition were significantly larger than controls at early time points, and this effect of delayed wound contraction in ROCK-inhibited wounds persisted for 7 days after wounding (P < 0.05). The effect of ROCK inhibition on delay of wound contraction was normalized at day 12. There was no significant difference between control and ROCK-inhibited groups in the area of the nascent epithelium beyond the wound margin, wound inflammatory cellular density, and TGF-β1 expression. However, ROCK inhibition led to as statistically significant decrease in α-SMA stress fiber formation compared to controls [32.5% (3.5%) vs 17.4% (2.6%); P < 0.05]. CONCLUSIONS: Local delivery of a ROCK inhibitor delayed the time course of murine wound contraction in a manner similar to that previously reported in α-SMA knock-out rodents, thus demonstrating an effective method for in vivo ROCK inhibition. Accordingly, α-SMA stress fiber formation was inhibited in treated wound beds without altering local inflammation, TGF-β1 expression, or epithelial wound edge advancement.

Original languageEnglish (US)
Pages (from-to)S213-S219
JournalAnnals of Plastic Surgery
Volume72
Issue numberSUPPL. 2
DOIs
StatePublished - Jun 2014

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Keywords

  • Rho-associated kinases
  • Scar
  • Wound contraction
  • Wound healing

ASJC Scopus subject areas

  • Surgery

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