Determination of growth factor and receptor levels in human skin from wound borders: implications for gene therapy to accelerate wound healing

2008 
The healing of wounds involves a wide range of cellular, molecular, physiological and biochemical events. Many studies have been reported whereby growth factors either singly (reviewed in Meyer-Ingold 1993), or in combination (Brown et al. 1994; Moulin 1998) have been shown to accelerate the healing of dermal wounds. All animal models currently used to date rely on studies drawn from acute models of injury; there being no animal model for chronic wounds. Recently the sphingolipid metabolite sphingosylphosphorylcholine (SPC) was shown to accelerate dermal healing in a murine diabetic (db/db) model (Sun et al. 1996). SPC and Sphingosine-1-phosphate (SPP) are high affinity ligands for the G-protein coupled receptor Edg-1 (Wakita et al. 1998) which has been implicated as a second messenger in cell proliferation and survival (reviewed in Goetzl & Songzhau 1999). To assist us in the design of a biological therapeutics program for wound healing, we have sought to determine the expression profile of a panel of growth factors and receptors in human skin. Using skin biopsy material from both healthy donors and patients with limb ulcerations, we have constructed a landscape plot of gene expression as determined by either immunohistochemistry or in situ hybridisation. When compared with samples from healthy individuals, we show upregulation of VEGF protein in the stratum spinosum, germunativum and granulosum and TGFb protein in the stratum spinosum. We also show significant upregulation of the Edg-1 receptor surrounding the blood vessels. Future studies include comparative analyses. In skin samples from venous ulcers (treated by good ulcer care or Dermapulse), arterial (diabetic) ulcers and pressure sores. Our strategies aimed at manipulating growth factor and receptor profile will be discussed.
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