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TGF-β Antisense Therapy Increases Angiogenic Potential in Human KeratinocytesIn Vitro∗

Authors
Journal
Archives of Medical Research
0188-4409
Publisher
Elsevier
Publication Date
Volume
38
Issue
1
Identifiers
DOI: 10.1016/j.arcmed.2006.04.010
Keywords
  • Keratinocytes
  • Chronic Wound
  • Vegf
  • Angiogenesis
  • Tgf-β
Disciplines
  • Biology
  • Chemistry
  • Medicine

Abstract

Background Transforming growth factor-beta (TGF-β) 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-β. The purpose of this study was to analyze the effect of TGF-β 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-β 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-β oligonucleotide treatment upregulated VEGF secretion in vitro. Addition of conditioned medium from TGF-β antisense-treated keratinocytes resulted in an increase of endothelial cell migration and tube formation. Conclusions Our results demonstrate that TGF-β antisense oligonucleotide technology may be a potential therapeutic option for stimulation of angiogenesis in chronic wounds.

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