調制膠原蛋白合成瘢痕疙瘩的沉默smad2有抑制作用.

倒序瀏覽 · 發(fā)表于 2007-4-28 22:32:39

背景:keloids代表dysregulated回應傷人皮膚造成過多的細胞外基質沉積,特別是第一型和第三型膠原. Transforming growth factor (TGF)-beta plays a central role in the pathogenesis of fibrosis by inducing and sustaining activation of keloid fibroblast.轉化生長因子(TGF)beta發(fā)揮著核心作用,發(fā)病纖維化誘導和激活身受瘢痕疙瘩纖維. However, the underlying mechanisms are poorly understood.不過,基本的機制仍不甚清楚. In this study, the authors examined the function of Smad2, a recently characterized intracellular effector of TGF-beta signaling, in keloid fibroblasts using small interfering RNA (siRNA).在這項研究中,作者研究的功能smad2,最近一個特點effector內的TGF-信令瘢痕疙瘩利用小干擾RNA(siRNA). METHODS: Three pairs of siRNA duplexes targeting human Smad2 were designed; the most efficient one was selected and used for further research.方法:三組的siRNAduplexes針對人類smad2設計;最有效率的一個已經(jīng)選定,并作進一步的研究. Keloid fibroblasts were treated with or without Smad2 siRNA, and the expression levels of related genes were examined by reverse-transcriptase polymerase chain reaction and immunofluorescence.瘢痕疙瘩患者或無smad2sirna,而表達水平的相關基因,研究反轉錄聚合酶鏈反應和免疫. RESULTS: The down-regulation of Smad2 by siRNA led to a significant decrease in mRNA levels of Smad2 in both a dose-dependent and time-dependent manner.結果:下調smad2抑制作用顯著降低轉錄水平smad2兩種劑量依賴性和時間依賴性. The knockdown of Smad2 expression in protein level was confirmed using immunofluorescence.擊倒Smad2表達蛋白水平證實,用免疫. The mRNA levels of types I and III procollagen were also significantly and uniquely decreased following the reduction of Smad2 by siRNA.mRNA水平的第一型和第三型膠原也顯別致下跌后減少smad2抑制作用. CONCLUSIONS: The results indicate that Smad2 plays an important role in TGF-beta-induced fibrosis in keloids.結論:結果顯示smad2起著重要作用,在涉及TGF-致纖維化瘢痕疙瘩. Down-regulation of Smad2 expression in keloid fibroblasts can significantly decrease procollagen gene expression.下調Smad2表達瘢痕疙瘩可顯著降低膠原基因的表達. Also, siRNA targeting Smad2 was an efficient reagent with which to reduce extracellular matrix deposition and attenuate process of fibrosis.還的siRNAsmad2是一種很有效的試劑,來減少外基質沉積及衰減過程纖維化. It could be a new, promising therapeutic approach for improving skin wound healing and inhibiting progression of fibrotic conditions by interrupting the TGF-beta signaling pathway.它可能是一種新的大有希望的治療方法,增進傷口愈合及抑制艾滋fibrotic條件打斷了轉化生長因子信號通路.