Effect of interferon‐α2b on guinea pig wound closure and the expression of cytoskeletal proteins in vivo

Publisher Website
Google Scholar
Abstract
Scar contraction following the healing of deep partial‐thickness or full‐thickness dermal injury is a leading cause of functional and cosmetic morbidity. The therapeutic use of interferon for the treatment of fibroproliferative disorders associated with scar contraction, including hypertrophic scar, has been suggested because of its antifibrotic properties. Treatment of fibroblasts with interferon has been shown to reduce the rate and extent of contraction using the in vitro fibroblast‐populated collagen lattice model. In order to establish the effect of interferon‐α2b on full‐thickness wound contraction in vivo, osmotic pumps loaded with interferon or sterile saline were implanted intraperitoneally in guinea pigs. Seven days following implantation, six full‐thickness punch biopsy wounds were created and were monitored by daily assessment of the wound. There was a significant reduction in the rate of wound contraction in the interferon‐treated animals after day 3 (p < 0.01). Western blot analysis was used to quantitate selected cytoskeletal proteins in the normal skin and tissue biopsied from the wound at days 7, 14, and 21 postinjury. The amount of vimentin in the contracted wound increased following injury as compared with the amount present in normal skin (p < 0.0001); however, the relative amounts of the myofibroblast‐associated cytoskeletal proteins α‐smooth muscle actin and smooth muscle myosin were less than those found in normal, uninjured skin. By using vimentin to adjust the levels of cytoskeletal proteins for the increase in cellularity in the wounds, both α‐smooth muscle actin and smooth muscle myosin significantly increased after closure of the wounds on day 14, as compared with the open‐wound stage (day 7), before further reductions occurred with remodeling on day 21. Measurement of apoptotic cells using the terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labeling assay revealed an increase in apoptosis in the interferon‐α2b‐treated animals at 21 days following wounding (p < 0.001), which did not colocalize with α‐smooth muscle actin staining. Taken together, these findings suggest that interferon‐α2b inhibits wound contraction in vivo, not through an appreciable alteration in myofibroblast number or cytoskeletal protein expression, but possibly through a reduction in fibroblast cellularity by the induction of apoptosis.

This publication has 0 references indexed in Scilit: