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  • Title: Modulation of collagen synthesis in keloid fibroblasts by silencing Smad2 with siRNA.
    Author: Gao Z, Wang Z, Shi Y, Lin Z, Jiang H, Hou T, Wang Q, Yuan X, Zhao Y, Wu H, Jin Y.
    Journal: Plast Reconstr Surg; 2006 Nov; 118(6):1328-1337. PubMed ID: 17051103.
    Abstract:
    BACKGROUND: Keloids represent a dysregulated response to cutaneous wounding that results in an excessive deposition of extracellular matrix, especially types I and III collagen. Transforming growth factor (TGF)-beta plays a central role in the pathogenesis of fibrosis by inducing and sustaining activation of keloid fibroblast. However, the underlying mechanisms are poorly understood. 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). METHODS: Three pairs of siRNA duplexes targeting human Smad2 were designed; the most efficient one was selected and used for further research. 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. 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. The knockdown of Smad2 expression in protein level was confirmed using immunofluorescence. The mRNA levels of types I and III procollagen were also significantly and uniquely decreased following the reduction of Smad2 by siRNA. CONCLUSIONS: The results indicate that Smad2 plays an important role in TGF-beta-induced fibrosis in keloids. Down-regulation of Smad2 expression in keloid fibroblasts can significantly decrease procollagen gene expression. Also, siRNA targeting Smad2 was an efficient reagent with which to reduce extracellular matrix deposition and attenuate process of fibrosis. 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.
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