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  • Title: TGF-ß1 antisense impacts the SMAD signalling system in fibroblasts from keloid scars.
    Author: Bran GM, Sommer UJ, Goessler UR, Hörmann K, Riedel F, Sadick H.
    Journal: Anticancer Res; 2010 Sep; 30(9):3459-63. PubMed ID: 20944123.
    Abstract:
    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.
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