TGF-ß1 antisense impacts the SMAD signalling system in fibroblasts from keloid scars.

AIM To identify the effect of a TGF-β1 antisense treatment of keloid fibroblasts on the SMAD signalling system. MATERIAL AND METHODS In this cross-sectional study, keloid and adjacent healthy tissue was harvested from 9 patients with keloid scars after otoplasty. Keloid fibroblasts were placed in monolayer cultures. Expression of SMAD2, -3, -4, -6, and SMURF2 were analysed by immunohistochemistry. Analysis of treatment with antisense oligonucleotides was conducted by immunohistochemistry, and RT-PCR. RESULTS Immunohistochemical investigation demonstrated increased expression of SMAD2, -3 and -4, and decreased expression of SMURF2. TGF-β1 antisense therapy significantly down-regulated SMAD2 and SMAD4, up-regulated SMURF2 and showed no effect on SMAD3 and SMAD6. CONCLUSION TGF-β1 led to elevated levels of the SMAD signalling cascade, indicating an abnormal sensitivity of keloid-derived fibroblasts to this cytokine. Abrogation correlated with potential suppression of the fibro-proliferative progress. There is growing evidence for an abnormal response to this cytokine in the intracellular signal transduction in keloid-derived fibroblasts.