调制胶原蛋白合成瘢痕疙瘩的沉默smad2有抑制作用.

阅读模式 · 发表于 2007-4-28 22:32:39

背景:keloids代表dysregulated回应伤人皮肤造成过多的细胞外基质沉积,特别是第一型和第三型胶原. Transforming growth factor (TGF)-beta plays a central role in the pathogenesis of fibrosis by inducing and sustaining activation of keloid fibroblast.转化生长因子(TGF)beta发挥着核心作用,发病纤维化诱导和激活身受瘢痕疙瘩纤维. However, the underlying mechanisms are poorly understood.不过,基本的机制仍不甚清楚. 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).在这项研究中,作者研究的功能smad2,最近一个特点effector内的TGF-信令瘢痕疙瘩利用小干扰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:三组的siRNAduplexes针对人类smad2设计;最有效率的一个已经选定,并作进一步的研究. 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.瘢痕疙瘩患者或无smad2sirna,而表达水平的相关基因,研究反转录聚合酶链反应和免疫. 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.结果:下调smad2抑制作用显着降低转录水平smad2两种剂量依赖性和时间依赖性. The knockdown of Smad2 expression in protein level was confirmed using immunofluorescence.击倒Smad2表达蛋白水平证实,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胶原也显别致下跌后减少smad2抑制作用. CONCLUSIONS: The results indicate that Smad2 plays an important role in TGF-beta-induced fibrosis in keloids.结论:结果显示smad2起着重要作用,在涉及TGF-致纤维化瘢痕疙瘩. Down-regulation of Smad2 expression in keloid fibroblasts can significantly decrease procollagen gene expression.下调Smad2表达瘢痕疙瘩可显着降低胶原基因的表达. Also, siRNA targeting Smad2 was an efficient reagent with which to reduce extracellular matrix deposition and attenuate process of fibrosis.还的siRNAsmad2是一种很有效的试剂,来减少外基质沉积及衰减过程纤维化. 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.它可能是一种新的大有希望的治疗方法,增进伤口愈合及抑制艾滋fibrotic条件打断了转化生长因子信号通路.