title: [Mechanism underlying the inhibitory effects of peroxisome proliferator-activated receptor γ agonists on transforming growth factor β1 in adult skin fibroblasts].
abstract: OBJECTIVE
  To study the mechanism underlying the inhibitory effects of peroxisome proliferator-activated receptor γ (PPARγ) agonists on transforming growth factor β1 (TGF-β(1))-induced scarring of skin.
  
  
  METHODS
  Fibroblasts isolated from healthy adult skin were cultured in vitro and divided into blank control group (serum-free DMEM culture), TGF-β(1) group (with stimulation of 10 ng/mL TGF-β(1) for 48 hours), troglitazone group (with the same treatment as in TGF-β(1) group after stimulation of 10 µmol/L troglitazone for 2 hours), and 15-dioxygen prostaglandin J2 (15d-PGJ2) group (with the same treatment as in TGF-β(1) group after stimulation of 10 µmol/L 15d-PGJ2 for 2 hours) according to the stimulation added into DMEM. The expression of connective tissue growth factor (CTGF) was determined with Western blot. The mRNA levels of CTGF, matrix metalloproteinase-1 (MMP-1) and platelet-derived growth factor (PDGF) were determined with real-time fluorescence RT-PCR. Data were processed with one-way analysis of variance.
  
  
  RESULTS
  The expression of CTGF at mRNA and protein levels in skin fibroblasts were significantly increased in TGF-β(1) group as compared with control group; while expression of CTGF at mRNA and protein levels in 15d-PGJ2 and troglitazone groups were significantly decreased as compared with that in TGF-β(1) group. The mRNA level of MMP-1 in TGF-β(1) group (0.193 ± 0.051) was obviously lower than that in blank control group (1.281 ± 0.195, F = 12.811, P < 0.01), while the mRNA levels of MMP-1 in troglitazone group (0.417 ± 0.043) and 15d-PGJ2 group (0.485 ± 0.027) were significantly increased as compared with that in TGF-β(1) group (F = 12.811, P values all below 0.01). The mRNA level of PDGF in TGF-β(1) group (1.044 ± 0.237) was obviously higher than that in control group (0.349 ± 0.057, F = 16.848, P < 0.01), while the levels in troglitazone group (0.677 ± 0.055) and 15d-PGJ2 group (0.511 ± 0.017) were significantly decreased as compared with that in TGF-β(1) group (F = 16.848, P values all below 0.01).
  
  
  CONCLUSIONS
  The inhibitory effect of activated PPARγ on the expression of CTGF induced by TGF-β(1) may be the main mechanism of its inhibitory effect on TGF-β(1)-induced scarring on skin, and its influence on MMP-1 and PDGF may also be one of the underlying mechanisms.
authors.affiliation: Burn Center, the 322ed Hospital of PLA, Datong 037006, China.
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Yang
authors.forename: Hui-Tang
authors.initials: HT
authors.lastname: Zhang
authors.forename: Gong-Sheng
authors.initials: GS
authors.lastname: Wang
authors.forename: Hai-Quan
authors.initials: HQ
authors.lastname: Zhou
authors.forename: Chi
authors.initials: C
authors.lastname: Ma
authors.forename: Da-Hai
authors.initials: DH
authors.lastname: Hu
mesh_terms: D002460:Cell Line; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D047495:PPAR gamma; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1