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H. Paul Ehrlich, PhD; Kerry A. Keefer, MS; Roland L. Myers, MS; Anthony Passaniti, PhD

Arch Surg. 1999;134:494-501.

Hypothesis  Fibroblasts, not myofibroblasts, are responsible for wound contraction. Only myofibroblasts express a smooth muscle actin for which vanadate blocks its expression. Wound contraction in vanadate-treated rats will proceed normally in the absence of myofibroblasts.

Design  Laboratory study using rats.

Methods  Wound healing in rats receiving vanadate parenterally, an inhibitor of tyrosine phosphate phosphatases, was investigated. For 21 days, treated rats received drinking water containing vanadate, 0.2 mg/mL, in isotonic sodium chloride solution, and the control rats received isotonic sodium chloride solution alone. On day 7, 4 square, full-excision wounds were made dorsally 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 measured 7.1±1.8 U (mean±SD), and the wound area in the control rats measured 7.2±2.2 U. The control rats' granulation tissue (GT) had myofibroblasts, or -smooth muscle (-SM) actin-positive fibroblasts, whereas the vanadate-treated group's fibroblasts were devoid of -SM actin. By Western blot analysis, GT homogenates in the vanadate-treated group contained less -SM actin. By electron microscopy, control rats' GT showed classic myofibroblast populations, and the collagen fiber bundles were randomly organized. In contrast, the wounds in the vanadate-treated group showed unencumbered fibroblast populations and neatly ordered, parallel collagen fiber bundles. By polarized light microscopy, the GT of the vanadate-treated group displayed orderly collagen fiber bundles.

Conclusions  The differentiation of fibroblasts into myofibroblasts requires the dephosphorylation of selected tyrosine phosphate residues. In the absence of myofibroblasts, the rate of rat wound contraction is normal, and collagen fiber bundles have a more orderly arrangement. Myofibroblasts are not required for wound contraction.

From the Division of Plastic Surgery, Departments of Surgery (Dr Ehrlich and Mr Keefer) and Neurosciences and Anatomy (Mr Myers), Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey; and the Laboratory of Biological Chemistry, National Institute on Aging, Baltimore, Md (Dr Passaniti).

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