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Int J Mol Med ; 22(1): 55-60, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18575776

ABSTRACT

Transforming growth factor-beta1 (TGF-beta1) 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-beta1. The purpose of this study was to analyze the effect of TGF-beta1 targeting on the expression of matrix metalloproteinases (MMPs) 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-beta1 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-beta1 oligonucleotide treatment significantly downregulated MMP-9 secretion in vitro. In conclusion, TGF-beta1 antisense oligonucleotide technology may be a potential therapeutic option for the inhibition of proteolytic tissue destruction in keloids.


Subject(s)
Fibroblasts/drug effects , Fibroblasts/enzymology , Keloid/enzymology , Keloid/pathology , Matrix Metalloproteinases/metabolism , Oligonucleotides, Antisense/pharmacology , Transforming Growth Factor beta1/antagonists & inhibitors , Fibroblasts/pathology , Gene Expression Regulation, Enzymologic/drug effects , Humans , Immunohistochemistry , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Subcellular Fractions
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