Expression of Smad protein by normal skin fibroblasts and hypertrophic scar fibroblasts in response to transforming growth factor beta1.
BACKGROUND
Smad proteins are important intracellular mediators of transforming growth factor (TGF)-beta signaling. Little has been known about the specific relationship between TGF-beta and TGF-beta/Smad signaling in hypertrophic scars.


OBJECTIVE
The objective was to investigate the expression of Smads and the specific relationship between TGF-beta and TGF-beta/Smad signaling in hypertrophic scars.


METHODS
In this study, we initially determined the endogenous protein levels of Smad2 and Smad7 in hypertrophic scar fibroblast (HSFs) and normal skin fibroblast (NSFs). Second, we stimulated HSFs and NSFs with recombinant human TGF-beta1 for 24 hours to determine whether the TGF-beta1 could potentiate its effect by further stimulating the production of Smad by reverse transcription-polymerase chain reaction and Western blot analysis.


RESULTS
When compared with NSFs, the endogenous expression of Smad2 in HSFs was up-regulated and TGF-beta1 could further stimulate the production of Smad2. Although the levels of Smad7 were similar between HSFs and NSFs, TGF-beta1 up-regulated the expression of Smad7 for NSFs only, with no discernible effect on HSFs. These changes were paralleled by a significant increase in cytoplasm-to-nuclear translocation of Smad2.


CONCLUSIONS
These data substantiated the model of an autocrine positive loop in hypertrophic scars pathogenesis. The authors have indicated no significant interest with commercial supporters.
Xie
Ju-lin
JL
Department of Burns, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, PR China.
Qi
Shao-hai
SH
Pan
Shu
S
Xu
Ying-bin
YB
Li
Tian-zeng
TZ
Liu
Xu-sheng
XS
Liu
Po
P
D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D012867:Skin / Q000378:metabolism*; D051899:Smad2 Protein / Q000737:chemistry / Q000378:metabolism*; D051906:Smad7 Protein / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000378:metabolism*; D015854:Up-Regulation
C497782:SMAD2 protein, human; C497806:SMAD7 protein, human; D051899:Smad2 Protein; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1