Abstract
Problem
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 metallo-proteinases (MMP-2 and MMP-9) in fibroblasts cultured from earlobe keloids.
Methods
The expression of MMP-2 and MMP-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 analyzed by ELISA and multiplex RT-PCR.
Results
Immunohistochemical studies demonstrated an increased expression of MMP-2 and MMP-9 proteins in tissue samples from keloids compared to normal human skin. The treatment of human keloid-derived fibroblasts with TGF-beta1 antisense oligonucleotides (ONDs) in vitro efficiently down-regulated MMP-9 expression but not the MMP-2 expression. In the supernatans of keloid-derived fibroblasts, the TGF-beta1 antisense therapy showed a decreased secretion level of both MMP-9 and MMP-2. So other than in MMP-9, the synthesis of MMP-2 does not seem to be influenced by TGF-beta1 anti-sense ONDs whereas the secretion of MMP-2, similar to that of MMP-9, is significantly decreased in the supernatans of keloid-derived fibroblasts.
Conclusion
TGF-beta1 antisense OND technology may be a potential therapeutic option for the inhibition of proteolytic tissue destruction in keloids. The results should be regarded as a further implication for the possible treatment of keloids.
Significance
The results should be regarded as a further implication for the possible treatment of keloids.
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