Inhibiting scar formation in vitro and in vivo by adenovirus-mediated mutant Smad4: a preliminary report.

Abstract:

:The best characterized signalling pathway employed by transforming growth factor-beta (TGF-β) is the Smad pathway. We focused on Smad4, because it is essential for the activation of Smad-dependent target genes. We aimed to explore the possibility of inhibiting scar formation after wounding by blocking TGF-β signalling by means of a gene therapy approach using adenovirus-mediated expression of mutant Smad4. The coding sequence of the dominant-negative mutant Smad4ΔM4, which has a deletion in the linker region of Δ275-322, was introduced by homologous recombination into an adenovirus vector to generate the recombinant vector Ad-ΔM4, which encoded Smad4ΔM4. Mouse fibroblast NIH 3T3 cells were transfected with Ad-ΔM4 and cell proliferation, collagen protein production, and the expression of collagen type I and type III mRNA were evaluated in vitro using a cell proliferation test, western blot analysis, and RT-PCR, respectively. Cell proliferation and the expression of collagen type I and type III mRNA and protein were all inhibited by the transfection of Ad-ΔM4. In vivo, Ad-ΔM4 was applied externally to wounds on rats, and histological examination and quantification of the scars were performed to evaluate the curative effect. The transfection of Ad-ΔM4 successfully inhibited scar formation in rat wounds. In conclusion, Ad-ΔM4 can block the TGF-β signalling of mouse wound cells effectively. In addition, gene therapy with Ad-ΔM4 can effectively inhibit wound scarring in rats and may potentially be applied to clinical treatment of scars.

journal_name

Exp Dermatol

journal_title

Experimental dermatology

authors

Tan WQ,Gao ZJ,Xu JH,Yao HP

doi

10.1111/j.1600-0625.2010.01186.x

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

119-24

issue

2

eissn

0906-6705

issn

1600-0625

journal_volume

20

pub_type

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