Activation of peroxisome proliferator-activated receptor-gamma inhibits transforming growth factor-beta1 induction of connective tissue growth factor and extracellular matrix in hypertrophic scar fibroblasts in vitro.
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands have been recently reported to have beneficial effects on organ fibrosis. However, their effects on extracellular matrix (ECM) turnover in hypertrophic scar fibroblasts (HSFs), and the related molecular mechanisms are unknown. HSFs were cultured and exposed to different concentration PPAR-gamma ligands in the presence of transforming growth factor-beta1 (TGF-beta1). In growth-arrested HSFs, a PPAR-gamma natural ligand (15-deoxy-D12,14-prostaglandin J2, 15d-PGJ2) and a synthetic ligand (GW7845) dose-dependently attenuated TGFbeta1-induced expression of Connective tissue growth factor (CTGF), collagens and fibronectin. Furthermore, the suppression of CTGF mRNA and protein expression are relieved by pretreatment with an antagonist of PPAR-gamma (GW9662). Moreover, GW7845 and 15d-PGJ2 partially inhibited the expression and phosphorylation of the TGF-beta1/Smad pathway. These results suggest that in TGFbeta1-stimulated HSFs, PPAR-gamma ligands caused an antiproliferative effect and reduced ECM production through mechanisms that included reducing CTGF expression, and a crosstalk between PPAR-gamma and Smad may be involved in the inhibitory effects of PPAR-gamma ligands.
Zhang
Guo-You
GY
Department of Hand and Plastic Surgery, The 2nd Affiliated Hospital of Wenzhou Medical College, Xueyuan West Road 109#, 325027 Wenzhou, Zhejiang, China.
Cheng
Tao
T
Zheng
Ming-Hua
MH
Yi
Cheng-Gang
CG
Pan
Hua
H
Li
Zhi-Jie
ZJ
Chen
Xing-Long
XL
Yu
Qing
Q
Jiang
Liang-Fu
LF
Zhou
Fei-Ya
FY
Li
Xiao-Yang
XY
Yang
Jing-Quan
JQ
Chu
Ting-Gang
TG
Gao
Wei-Yang
WY
D048708:Cell Growth Processes / Q000187:drug effects; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003238:Connective Tissue / Q000473:pathology; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D005109:Extracellular Matrix; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D010080:Oxazoles / Q000494:pharmacology; D047495:PPAR gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
C477819:15-deoxyprostaglandin J2; D010080:Oxazoles; D047495:PPAR gamma; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; C401311:GW 7845; D014443:Tyrosine; D015230:Prostaglandin D2