title: [Rosiglitazone inhibited the transformation and synthesis of collagen in rats' embryonic lung fibroblasts through the modulation of plasminogen activator inhibitor-1].
abstract: OBJECTIVE
  To investigate the role of plasminogen activator inhibitor-1 (PAI-1) in the inhibition of rosiglitazone on the transformation and collagen synthesis of rats' embryo lung fibroblasts and to examine the signal pathways in the process.
  
  
  METHODS
  Fibroblasts from rats' embryo lung tissues were divided into 3 groups: Control, Rosiglitazone (Rosiglitazone 30 mmol/L) and PAI-1 (Rosiglitazone 30 mmol/L and PAI-1 20 mmol/L) groups. The fibroblasts were collected at 24, 48 and 72 h, and stored at -80 °C. RT-PCR was used to determine the expressions of collagen type-1 and type-3 at 24 h. Western blot analysis was used to determine the expressions of PAI-1, a-smooth muscle actin (α-SMA), p-AKT and p-ERK at 24, 48 and 72 h.
  
  
  RESULTS
  There was a significant decrease in the protein expression of PAI-1 in the Rosiglitazone group (0.732±0.015, 0.583±0.005, 0.762±0.032) at 24, 48 and 72 h compared with the Control group (1.116±0.046). There was a significant increase in the protein expression in the PAI-1 group (0.923±0.042, 1.024±0.009, 1.070±0.011) compared with the Rosiglitazone group (F=78.609, P<0.01). The α-SMA protein expressions were significantly reduced in the Rosiglitazone group (0.209±0.012, 0.280±0.140, 0.254±0.025) compared with the Control group (0.340±0.026), while the expressions were significantly increased in the PAI-1 group (0.386±0.042, 0.400±0.037, 0.385±0.026) compared with the Rosiglitazone group (F=35.009, P<0.01). The collagen type-1 (1.065±0.004) and type-3 (1.282±0.001) mRNA expressions were significantly reduced in the Rosiglitazone group compared with the Control group (1.279±0.013, 1.690±0.005), while the expressions were significantly increased in the PAI-1 groups (1.390±0.029, 1.350±0.044) compared with the Rosiglitazone group (type-1: F=12.429, P<0.01; type-3: F=127.456, P<0.01). The expressions of p-AKT showed no differences among the 3 groups, but there were significant differences in the expressions of p-ERK in the Rosiglitazone group (0.288±0.010, 0.311±0.034, 0.336±0.038) compared with the Control group (0.506±0.032), and in PAI-1 groups (0.561±0.101, 0.448±0.022, 0.406±0.003) compared with the Rosiglitazone group (F=153.548, P<0.01).
  
  
  CONCLUSIONS
  Rosiglitazone inhibits PAI-1 expression in fibroblasts from rats' embryo lung tissues and activates the fibrinolytic system. The up-regulation of PAI-1 expression alleviates the inhibition effect of rosiglitazone on the transformation and collagen synthesis of fibroblasts. The cross-talk between PAI-1 and ERK signal pathway may play an important role in the regulation of rosiglitazone on fibrosis.
authors.affiliation: Department of Respiratory Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhang
authors.forename: Linlin
authors.initials: L
authors.lastname: Bai
authors.forename: Lihua
authors.initials: L
authors.lastname: Ma
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Wenbin
authors.initials: W
authors.lastname: Li
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis*; D024061:Collagen Type III / Q000096:biosynthesis*; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008168:Lung / Q000166:cytology; D020935:MAP Kinase Signaling System; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D051381:Rats; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D000199:Actins; D024042:Collagen Type I; D024061:Collagen Type III; D017395:Plasminogen Activator Inhibitor 1; D000077154:Rosiglitazone; D045162:Thiazolidinediones; C498862:Acta2 protein, rat