027 Exogenous Administration of SMAD3 by an Adenoviral Vector Significantly Affects Ischemic Tissue Repair

Abstract

Introduction: Chronic, nonhealing wounds are often observed in tissues with poor oxygen supply. Impaired reepithelialization is a hallmark of these wounds; however, the pathogenesis of the retarded reepithelialization in chronic, ischemic wounds remains poorly understood. Transforming Growth Factor beta (TGF-beta) is involved in both normal and hypoxic wound healing response and exogenous overexpression of Smad3, a TGF-beta signaling intermediate, has been known to accelerate reepithelialization. In a recent study, Ad-Smad3 injection in the rabbit ear dermal ulcer model showed enhanced reepithelialization and granulation tissue area suggesting a positive effect of Smad3 on wound healing. However, little is known about the role of Smad3 in the ischemic wound healing process. In this study we examined the effect of Smad3 in an ischemic wound model. Methods: Ad-Smad3 or LacZ (108 pfu/wound) empty vector was injected in either ear of White New Zealand Rabbits. Twenty-four hours later, these ears were rendered ischemic using an established model and four 7-mm full-thickness punch wounds were made on each ear. Results: Histological evaluation showed a highly significant increase in reepithelialization, epithelial ingrowth and percentage of epithelialization in Ad-Smad3 transfected wounds versus ischemic wounds transfected with LacZ-empty vector (p < 0.01). Conclusion: Our data confirm the enhancing effect of Smad3 on reepithelialization in an ischemic wound model. The deficiency in reepithelialization, as evident in chronic ischemic wounds, could thus be ameliorated by excess Smad3. Therapeutic interventions using overexpressed Smad3 may improve wound healing through accelerated epithelialization in chronic wounds.