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Decreased expression of inhibitory SMAD6 and SMAD7 in keloid scarring

Keloids are benign skin tumours occurring during wound healing 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 (TGFβ) is involved in keloid formati...

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Published in:Journal of plastic, reconstructive & aesthetic surgery reconstructive & aesthetic surgery, 2006-01, Vol.59 (3), p.221-229
Main Authors: Yu, Haiyan, Bock, Oliver, Bayat, Ardeshir, Ferguson, Mark W.J., Mrowietz, Ulrich
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cited_by cdi_FETCH-LOGICAL-c487t-40bf885adb1268c0497bff61b401bd9abf140cfbfb7a39786f8bf1b3f22da48b3
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creator Yu, Haiyan
Bock, Oliver
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description Keloids are benign skin tumours occurring during wound healing 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 (TGFβ) is involved in keloid formation. SMAD proteins play a crucial role in TGFβ signaling and in terminating the TGFβ signal by a negative feedback loop through SMAD6 and 7. It is unclear how TGFβ 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. Cells were stimulated with TGFβ1 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
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They are characterised by an abnormal deposition of extracellular matrix components, in particular collagen. There is evidence that transforming growth factor-beta (TGFβ) is involved in keloid formation. SMAD proteins play a crucial role in TGFβ signaling and in terminating the TGFβ signal by a negative feedback loop through SMAD6 and 7. It is unclear how TGFβ 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. Cells were stimulated with TGFβ1 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&lt;0.01) and normal skin fibroblasts ( p&lt;0.05). SMAD3 mRNA was found to be lower in keloids ( p&lt;0.01) and in normal scar fibroblasts ( p&lt;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 TGFβ signaling is not terminated in keloids leading to overexpression of extracellularmatrix in keloids. 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They are characterised by an abnormal deposition of extracellular matrix components, in particular collagen. There is evidence that transforming growth factor-beta (TGFβ) is involved in keloid formation. SMAD proteins play a crucial role in TGFβ signaling and in terminating the TGFβ signal by a negative feedback loop through SMAD6 and 7. It is unclear how TGFβ 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. Cells were stimulated with TGFβ1 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&lt;0.01) and normal skin fibroblasts ( p&lt;0.05). SMAD3 mRNA was found to be lower in keloids ( p&lt;0.01) and in normal scar fibroblasts ( p&lt;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 TGFβ signaling is not terminated in keloids leading to overexpression of extracellularmatrix in keloids. 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identifier ISSN: 1748-6815
ispartof Journal of plastic, reconstructive & aesthetic surgery, 2006-01, Vol.59 (3), p.221-229
issn 1748-6815
1878-0539
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source ScienceDirect Journals
subjects Biological and medical sciences
Blotting, Western
Cells, Cultured
Dermatology
Fibroblasts - metabolism
Humans
Keloid - metabolism
Keloids
Medical sciences
MEDICIN
MEDICINE
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
Skin involvement in other diseases. Miscellaneous. General aspects
SMAD
Smad6 Protein - metabolism
Smad7 Protein - metabolism
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
TGFβ
TGFβ signalling
Transforming Growth Factor beta - pharmacology
Transforming Growth Factor beta1
title Decreased expression of inhibitory SMAD6 and SMAD7 in keloid scarring
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