TGF-β1 antisense therapy modulates expression of matrix metalloproteinases in keloid-derived fibroblasts

Abstract

Transforming growtli factor-β1 (TGF-β1) has been identified as an important regulator of wound healing. Recent developments in molecular therapy offer exciting prospects for the modulation of wound healing, specifically those targeting TGF-β1. The purpose of this study was to analyze the effect of TGF-β1 targeting on the expression of matrix metalloproteinases (NMPs) in fibroblasts cultured from earlobe keloids. The expression of MMP-2 and -9 in tissue samples from keloids was investigated by immunohistochemistry. The effect of TGF-β1 targeting using antisense oligonucleotides on the expression of MMPs in keloid-derived fibroblasts was analysed by ELISA and multiplex RT-PCR. Immunohistochemical studies demonstrated an increased expression of MMP protein in tissue samples from keloids compared to normal human skin. Antisense TGF-β1 oligonucleotide treatment significantly downregulated MMP-9 secretion in vitro. In conclusion, TGF-β1 antisense oligonucleotide technology may be a potential therapeutic option for the inhibition of proteolytic tissue destruction in keloids.