Disequilibrium of dermal wound repair can result in continued accumulation of ECM and excessive scar formation. In susceptible genetically predisposed individuals, keloid formation can be observed. Keloid disease represents a benign dermal fibroproliferative tumor that is unique to humans. TGF-β is known to play a key role in the pathogenesis of this disease which is still not fully understood. The isoforms TGF-β1 and TGF-β2 have profibrotic properties, whereas TGF-β3 may have antifibrotic functions. TGF-β exerts its influence by binding to type I and type II TGF-β receptors, thereby forming a complex and activating specific downstream effector molecules. The aim of this study was to investigate the effect of TGF-β1 targeting by antisense oligonucleotides on the RNA synthesis and protein expression of TGF-β isoforms and their receptors in keloid-derived fibroblasts. In tissue samples with normal fibroblasts (NFs) serving as control samples, expression of TGF-β1 and -β2 was decreased when compared to keloid fibroblasts (KFs), while expression of TGF-β3 and of TGF-βRII was significantly higher in NFs. In the ELISA assay, abrogation of TGF-β1 led to a significant decrease in TGF-β1 and -β2 (p<0.05). Expression of TGF-β2 mRNA was reduced. Expression of TGF-β3 mRNA revealed contrary patterns in KFs from different patients while expression of TGF-βRI was found to be equal during the measurement period. TGF-βRII mRNA expression was increased after 48 and 72 h respectively. There is growing evidence for a regulatory mechanism between TGF-β1 and its receptors. Our findings support this theory by suggesting interrelations between the different TGF-β isoforms and their receptors. Abnormal response of KFs to TGF-βmight reflect a modification in the regulatory pathway that occurs at the receptor level or during intracellular trans-duction. Improving the understanding of TGF-β in keloid disease could lead to the development of clinically useful therapeutic modalities for treatment of keloid disease or even allow identification of preventive strategies.

Related Articles