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[Role and underlying mechanism of IGF-I/ERK signaling pathway in lung fibrosis].
- Source :
-
Zhonghua yi xue za zhi [Zhonghua Yi Xue Za Zhi] 2015 May 26; Vol. 95 (20), pp. 1615-8. - Publication Year :
- 2015
-
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.<br />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.<br />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).<br />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.
Details
- Language :
- Chinese
- ISSN :
- 0376-2491
- Volume :
- 95
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Zhonghua yi xue za zhi
- Publication Type :
- Academic Journal
- Accession number :
- 26463615