調(diào)制膠原蛋白合成瘢痕疙瘩的沉默smad2有抑制作用.

倒序?yàn)g覽 · 發(fā)表于 2007-4-28 22:32:39

背景:keloids代表dysregulated回應(yīng)傷人皮膚造成過(guò)多的細(xì)胞外基質(zhì)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(zhuǎn)化生長(zhǎng)因子(TGF)beta發(fā)揮著核心作用,發(fā)病纖維化誘導(dǎo)和激活身受瘢痕疙瘩纖維. However, the underlying mechanisms are poorly understood.不過(guò),基本的機(jī)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(xiàng)研究中,作者研究的功能smad2,最近一個(gè)特點(diǎn)effector內(nèi)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(duì)人類smad2設(shè)計(jì);最有效率的一個(gè)已經(jīng)選定,并作進(jìn)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(wú)smad2sirna,而表達(dá)水平的相關(guān)基因,研究反轉(zhuǎn)錄聚合酶鏈反應(yīng)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(jié)果:下調(diào)smad2抑制作用顯著降低轉(zhuǎn)錄水平smad2兩種劑量依賴性和時(shí)間依賴性. The knockdown of Smad2 expression in protein level was confirmed using immunofluorescence.擊倒Smad2表達(dá)蛋白水平證實(shí),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(jié)論:結(jié)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(diào)Smad2表達(dá)瘢痕疙瘩可顯著降低膠原基因的表達(dá). 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(lái)減少外基質(zhì)沉積及衰減過(guò)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(jìn)傷口愈合及抑制艾滋fibrotic條件打斷了轉(zhuǎn)化生長(zhǎng)因子信號(hào)通路.