title: 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.
abstract: 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.
authors.affiliation: Department of Hand and Plastic Surgery, The 2nd Affiliated Hospital of Wenzhou Medical College, Xueyuan West Road 109#, 325027 Wenzhou, Zhejiang, China.
authors.forename: Guo-You
authors.initials: GY
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Zheng
authors.forename: Cheng-Gang
authors.initials: CG
authors.lastname: Yi
authors.forename: Hua
authors.initials: H
authors.lastname: Pan
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Li
authors.forename: Xing-Long
authors.initials: XL
authors.lastname: Chen
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.forename: Liang-Fu
authors.initials: LF
authors.lastname: Jiang
authors.forename: Fei-Ya
authors.initials: FY
authors.lastname: Zhou
authors.forename: Xiao-Yang
authors.initials: XY
authors.lastname: Li
authors.forename: Jing-Quan
authors.initials: JQ
authors.lastname: Yang
authors.forename: Ting-Gang
authors.initials: TG
authors.lastname: Chu
authors.forename: Wei-Yang
authors.initials: WY
authors.lastname: Gao
mesh_terms: 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
chemical_list: 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