Inhibition of Smad3 expression decreases collagen synthesis in keloid disease fibroblasts

	Inhibition of Smad3 expression decreases collagen synthesis in keloid disease fibroblasts
	Wang, Z; Gao, Z; Shi, Y; Sun, Y; Lin, ZH; Jiang, H; Hou, TS; Wang, QG; Yuan, XB; Zhu, XH
刊名	JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY
	2007
卷号	60 期号:11 页码:1193-1199
关键词	RNA interference Smad3 keloid fibroblast
通讯作者	Wang, Z (reprint author), Second Mil Med Univ, Changhai Hosp, Dept Orthopaed, Shanghai 200433, Peoples R China.,wzmsmmu@yahoo.com.cn ; yxjin@sibs.ac.cn
英文摘要	Background: Keloids represent a dysregutated response to cutaneous wounding that result in an excessive deposition of extracellular matrix (ECM), especially types I and III collagen. In keloid scars, the ratio of 'type I to type III collagen' varies compared to normal skin. Transforming growth factor P (TGF-beta) plays a central role in the pathogenesis of fibrosis by inducing and sustaining activation of keloid fibroblasts. However, the underlying mechanisms are poorly understood. RNA interference (RNAi) is an evollutionally conserved mechanism for repressing targeted gene expression. In mammalian cells, RNAi is mediated by small interfering RNA (siRNA). In this paper, we examined the function of Sma and Drosophila mothers against decapentaptegic homotog 3 (Smad3), recently characterized as intracellular effector of TGF-beta signalling, in ketoid fibroblasts using siRNA. Methods: Dermal fibroblasts obtained from one female patient aged 21 years were maintained in Dulbecco's modified Eagle's medium. Cells (<6 passages) were treated with or without Smad3 siRNA and the expression levels of related genes were examined by Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western Blot. Statistical analysis was performed using one-way ANOVA (Dunnett correction) and the Excel 7.0 software, with significance set at p < 0.05. Results: The knockdown of Smad3 expression in mRNA and protein levels was confirmed using RT-PCR and Western Blot. Compared to blank, the mRNA levels of types I and III procoltagen were also significantly and uniquely decreased following the reduction of Smad3 by siRNA (p < 0.05). The results indicate that Smad3 plays an important role in the TGF-beta induced fibrosis in keloid. Downregutation of Smad3 expression in keloid fibroblasts can significantly decrease procollagen gene expression. SiRNA targeting Smad3 was an efficient reagent to reduce ECM deposition and attenuate process of fibrosis. It could be a new promising therapeutic approach to improve skin wound heating and inhibit progression of fibrotic conditions by interrupting the TGF-beta signal pathway. (C) 2006 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons.
学科主题	Surgery
类目[WOS]	Surgery
关键词[WOS]	GROWTH-FACTOR-BETA ; TGF-BETA ; TRANSCRIPTIONAL CONTROL ; HYPERTROPHIC SCAR ; MESSENGER-RNA ; TISSUE ; CELLS ; PHOSPHORYLATION ; TRIMERIZATION ; ACTIVATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000251039900004
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1615]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Wang, Z,Gao, Z,Shi, Y,et al. Inhibition of Smad3 expression decreases collagen synthesis in keloid disease fibroblasts[J]. JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY,2007,60(11):1193-1199.
APA	Wang, Z.,Gao, Z.,Shi, Y.,Sun, Y.,Lin, ZH.,...&Jin, YX.(2007).Inhibition of Smad3 expression decreases collagen synthesis in keloid disease fibroblasts.JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY,60(11),1193-1199.
MLA	Wang, Z,et al."Inhibition of Smad3 expression decreases collagen synthesis in keloid disease fibroblasts".JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY 60.11(2007):1193-1199.