Decreased expression of inhibitory SMAD6 and SMAD7 in keloid scarring

Keloids are benign skin tumours occurring during wound heating in genetically predisposed patients. They are characterised by an abnormal deposition of extracellular matrix components, in particular collagen. There is evidence that transforming growth factor-beta (TGF beta) is involved in keloid formation. SMAD proteins play a crucial role in TGF beta signaling and in terminating the TGF beta signal by a negative feedback loop through SMAD6 and 7. It is unclear how TGF beta signalling is connected to the pathogenesis of keloids. Therefore, we investigated the expression of SMAD mRNA and proteins in keloids, in normal skin and in normal scars. Dermal fibroblasts were obtained from punch-biopsies of keloids, normal scars and normal skin. Celts were stimulated with TGF beta 1 and the expression of SMAD2, 3, 4, 6 and 7 mRNA was analysed by real time RT-PCR. Protein expression was determined by Western blot analysis. Our data demonstrate a decreased mRNA expression of the inhibitory SMAD6 and 7 in keloid fibroblasts as compared to normal scar (p < 0.01) and normal skin fibroblasts (p < 0.05). SMAD3 mRNA was found to be tower in ketoids (p < 0.01) and in normal scar fibroblasts (p<0.001) compared to normal skin fibroblasts. Our data showed for the first time a decreased expression of the inhibitory SMAD6 and SMAD7 in keloid fibroblasts. This could explain why TGF beta signaling is not terminated in ketoids leading to overexpression of extracellularmatrix in keloids. These data support a possible rote of SMAD6 and 7 in the pathogenesis of ketoids. (C) 2005 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved.