Vanadate and the absence of myofibroblasts in wound contraction

Hypothesis: Fibroblasts, not myofibroblasts, are responsible for wound cont raction. Only myofibroblasts express a smooth muscle actin for which vanada te blocks its expression. Wound contraction in vanadate-treated rats will p roceed normally in the absence of myofibroblasts. Design: Laboratory study using rats. Methods: Wound healing in rats receiving vanadate parenterally, an inhibito r of tyrosine phosphate phosphatases, was investigated. For 21 days, treate d rats received drinking water containing vanadate, 0.2 mg/mL, in isotonic sodium chloride solution, and the control rats received isotonic sodium chl oride solution alone. On day 7, 4 square, full-excision wounds were made do rsally and measured, then 2 polyvinyl alcohol sponges were placed ventrally in subcutaneous pockets. Results: After 2 weeks, the wound area in the rats receiving vanadate measu red 7.1+/-1.8 U (mean+/-SD), and the wound area in the control rats measure d 7.2 +/- 2.2 U. The control rats' granulation tissue (GT) had myofibroblas ts, or alpha-smooth muscle (alpha-SM) actin-positive fibroblasts, whereas t he vanadate-treated group's fibroblasts were devoid of alpha-SM actin. By W estern blot analysis, GT homogenates in the vanadate-treated group containe d less alpha-SM actin. By electron microscopy, control rats' GT showed clas sic myofibroblast populations, and the collagen fiber bundles were randomly organized. In contrast, the wounds in the vanadate-treated group showed un encumbered fibroblast populations and neatly ordered, parallel collagen fib er bundles. By polarized light microscopy, the GT of the vanadate-treated g roup displayed orderly collagen fiber bundles. Conclusions: The differentiation of fibroblasts into myofibroblasts require s the dephosphorylation of selected tyrosine phosphate residues. In the abs ence of myofibroblasts, the rate of rat wound contraction is normal, and co llagen fiber bundles have a more orderly arrangement. Myofibroblasts are no t required for wound contraction.