TGF-beta antisense oligonucleotides modulate expression of matrix metalloproteinases in isolated fibroblasts from radiated skin.

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 matrix metalloproteinases (MMPs) in fibroblasts isolated from radiation-induced chronic dermal wounds. MATERIALS AND METHODS The expression of MMPs in tissue samples from radiation-induced chronic dermal wounds was investigated by immunohistochemistry and microarray technique. The effect of TGF-beta targeting using antisense oligonucleotides on the expression of MMPs in isolated fibroblasts was analysed by ELISA and multiplex RT-PCR. RESULTS Immunohistochemical investigation and microarray analysis demonstrated an increased expression of MMP protein and mRNA in tissue samples from radiation-induced chronic dermal wounds compared to normal human skin. Antisense TGF-beta oligonucleotide treatment significantly down-regulated MMP secretion in vitro. CONCLUSION TGF-beta antisense oligonucleotide technology may be a potential therapeutic option for the inhibition of proteolytic tissue destruction in radiation-induced chronic wounds.