Journal
ARCHIVES OF MEDICAL RESEARCH
Volume 38, Issue 1, Pages 45-51Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.arcmed.2006.04.010
Keywords
keratinocytes; chronic wound; VEGF; angiogenesis; TGF-beta
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Background. Transforming growth factor-beta (TGF-beta) has been identified as an important component of wound healing. Recent developments in molecular therapy offer exciting prospects for the modulation of wound healing, specifically those targeting TGF-beta. The purpose of this study was to analyze the effect of TGF-beta targeting on the expression of angiogenic vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, and in vitro angiogenic activity. Methods. Expression of angiogenic VEGF in tissue samples from chronic dermal wounds was investigated by immunohistochemistry. The effect of TGF-beta targeting using antisense oligonucleotides on the expression of VEGF was analyzed by ELISA and RT-PCR in cultured human keratinocytes. Human endothelial cells (EC) were grown in conditioned medium produced from the treated keratinocytes. EC migration was measured using a modified Boyden chamber, EC tube formation was analyzed under the light microscope. Results. Immunohistochemical investigation demonstrated a decreased expression of VEGF protein in tissue samples from chronic dermal wounds compared to normal human skin. Antisense TGF-beta oligonucleotide treatment upregulated VEGF secretion in vitro. Addition of conditioned medium from TGF-beta anti sense-treated keratinocytes resulted in an increase of endothelial cell migration and tube formation. Conclusions. Our results demonstrate that TGF-beta antisense oligonucleotide technology may be a potential therapeutic option for stimulation of angiogenesis in chronic wounds. (C) 2007 IMSS. Published by Elsevier Inc.
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