Comparative Analysis of Angiogenic Gene Expression in Normal and Impaired Wound Healing in Diabetic Mice: Effects of Extracorporeal Shock Wave Therapy
NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD
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Impaired wound healing is a persistent clinical problem which has been treated with mixed results. Studies aimed at elucidating the mechanism of impaired wound healing have focused on small cohorts of genes which leave an incomplete picture of the wound healing process. We aimed to investigate impaired wound healing via a comprehensive panel of angiogenicinflammation-related genes and wound closure kinetics with and without the application of extracorporeal shock wave therapy ESWT, which has been demonstrated to improve wound healing. Full-thickness skin from the dorsal surface of normal BALBc and impaired dbdb mice was excised, and wound margin tissue was harvested 2, 7, and 10 days post injury. A separate but identical wound model was established over 40 days in order to measure wound closure kinetics. Over time, the normal non-ESWT treated wounds exhibited varying patterns of elevated expression of 25-30 genes whereas wounds with impaired healing displayed prolonged elevated expression of only a few genes CXCL2, CXCL5 CSF3, MMP9, TGF-alpha. In response to ESWT, gene expression was augmented in both types of wounds, especially in the expression of PECAM-1 however, ESWT had no effect on wound closure in either model. In addition, multiple doses of ESWT exacerbated the delayed wound healing, and actually caused the wounds to initially increase in size. These data provide a more complete picture of impaired wound healing, and a way to evaluate various promising treatments.
- Medicine and Medical Research