title: [Role and underlying mechanism of IGF-I/ERK signaling pathway in lung fibrosis].
abstract: OBJECTIVE
  To explore the role and underlying mechanisms of insulin-like growth factor I (IGF-I)/extracellular signal-regulated kinase (ERK) signaling pathway in lung fibrosis.
  
  
  METHODS
  Alveolar epithelial cell A549 was used. The expressions of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in A549 culture media stimulated by IGF-I were determined by enzyme-linked immunosorbent assay (ELISA). ERK inhibitor U0126 was used. And there were three groups of control, IGF-I stimulation and RK inhibitor plus IGF-I stimulation. The activity of ERK in three groups was measured by Western blot. The mRNA level and protein concentration of MMP-2 and MMP-9 in three groups were examined by quantitative real-time-polymerase chain reaction (qRT-PCR) and ELISA.
  
  
  RESULTS
  The protein concentrations of MMP-2 and MMP-9 in cell culture media increased in 50, 100 ng/ml IGF-I groups as compared with 0 ng/ml IGF-I group ((18.30 ± 0.11), (21.80 ± 0.09) vs (13.52 ± 0.19) ng/ml and (0.34 ± 0.01), (0.39 ± 0.01) vs (0.25 ± 0.01) ng/ml, P < 0.001). And the protein concentrations of MMP-2 and MMP-9 in 100 ng/ml IGF-I group increased versus 50 ng/ml IGF-I group (P < 0.01). IGF-I stimulation group increased the expression of p-ERK1/2 versus control group (0.40 ± 0.01 vs 0.23 ± 0.02, P < 0.05) while ERK inhibitor plus IGF-I stimulation group decreased the expression of p-ERK1/2 versus IGF-I stimulation group (0.14 ± 0.03 vs 0.40 ± 0.01, P < 0.01). ERK inhibitor plus IGF-I stimulation group inhibited the mRNA levels of MMP-2 and MMP-9 versus IGF-I stimulation group (0.88 ± 0.03 vs 1.17 ± 0.05 and 0.82 ± 0.23 vs 1.81 ± 0.27, both P < 0.05) and decreased the concentrations of MMP-2 and MMP-9 in culture media versus IGF-I stimulation group ((21.70 ± 0.32) vs (29.15 ± 0.34) ng/ml and (0.22 ± 0.01) vs (0.29 ± 0.01) ng/ml, both P < 0.01).
  
  
  CONCLUSIONS
  IGF-I induces the expressions of MMP-2 and MMP-9 in alveolar epithelial cell through ERK signaling pathway. And it is associated with the disruption of epithelial basement membrane and the development of lung fibrosis.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing Institute of Respiratory Medicine, Beijing 100020, China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Li
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Geng
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Huang
authors.forename: Dingyuan
authors.initials: D
authors.lastname: Jiang
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Email: daihuaping@ccmu.edu.cn.
authors.forename: Huaping
authors.initials: H
authors.lastname: Dai
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases; D006801:Humans; D007334:Insulin-Like Growth Factor I; D020935:MAP Kinase Signaling System; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D012333:RNA, Messenger
chemical_list: D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D048049:Extracellular Signal-Regulated MAP Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9