RGD Reference Report - Inhibiting scar formation in vitro and in vivo by adenovirus-mediated mutant Smad4: a preliminary report. - Rat Genome Database

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

Authors: Tan, Wei-Qiang  Gao, Zheng-Jun  Xu, Jing-Hong  Yao, Hang-Ping 
Citation: Tan WQ, etal., Exp Dermatol. 2011 Feb;20(2):119-24. doi: 10.1111/j.1600-0625.2010.01186.x.
RGD ID: 12880045
Pubmed: PMID:21255090   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1600-0625.2010.01186.x   (Journal Full-text)

The best characterized signalling pathway employed by transforming growth factor-beta (TGF-ß) 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-ß signalling by means of a gene therapy approach using adenovirus-mediated expression of mutant Smad4. The coding sequence of the dominant-negative mutant Smad4¿M4, which has a deletion in the linker region of ¿275-322, was introduced by homologous recombination into an adenovirus vector to generate the recombinant vector Ad-¿M4, which encoded Smad4¿M4. Mouse fibroblast NIH 3T3 cells were transfected with Ad-¿M4 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-¿M4. In vivo, Ad-¿M4 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-¿M4 successfully inhibited scar formation in rat wounds. In conclusion, Ad-¿M4 can block the TGF-ß signalling of mouse wound cells effectively. In addition, gene therapy with Ad-¿M4 can effectively inhibit wound scarring in rats and may potentially be applied to clinical treatment of scars.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SMAD4HumanCicatrix treatmentISOSmad4 (Rattus norvegicus) RGD 
Smad4RatCicatrix treatmentIMP  RGD 
Smad4MouseCicatrix treatmentISOSmad4 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Smad4  (SMAD family member 4)

Genes (Mus musculus)
Smad4  (SMAD family member 4)

Genes (Homo sapiens)
SMAD4  (SMAD family member 4)


Additional Information