p38/ERK signal pathways regulating the expression of type I collagen and activity of MMP-2 in TGF-beta1-stimulated HLF-02 cells.
- Author:
Yong-bin HU
1
;
Yu-rong ZONG
;
De-yun FENG
;
Zhong-yuan JIN
;
Hai-ying JIANG
;
Jin-wu PENG
Author Information
- Publication Type:Journal Article
- MeSH: Blotting, Western; Cell Line; Collagen Type I; biosynthesis; genetics; Extracellular Signal-Regulated MAP Kinases; antagonists & inhibitors; physiology; Fibroblasts; drug effects; metabolism; Flavonoids; pharmacology; Humans; Imidazoles; pharmacology; Lung; cytology; Matrix Metalloproteinase 2; metabolism; Matrix Metalloproteinase 9; metabolism; Pyridines; pharmacology; RNA, Messenger; genetics; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; physiology; Transforming Growth Factor beta1; pharmacology; p38 Mitogen-Activated Protein Kinases; antagonists & inhibitors; physiology
- From: Chinese Journal of Industrial Hygiene and Occupational Diseases 2006;24(2):77-80
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the role of TGF-beta(1)/MAPK signaling pathways in the expression of type I collagen and activity of MMP-2, 9 in human lung fibroblasts.
METHODSHuman lung fibroblasts cell line (HLF-02) was cultured and and then stimulated with 10 ng/ml TGF-beta(1) for different time; SB203580 or PD98059 was added into culture medium to block p38 or ERK kinase pathway before incubated with TGF-beta(1); the expression of type I collagen was detected by Western blotting and RT-PCR; zymogram analysis was used to analyze the activity of MMP-2 and MMP-9.
RESULTS(1) In the process of stimulation by TGF-beta(1), the type I collagen mRNA level of 24 h, 48 h and 72 h group was: 1.33 +/- 0.07, 2.46 +/- 0.09 and 2.39 +/- 0.08 respectively; and the type I collagen protein level of 24 h, 48 h and 72 h group was: 114.89 +/- 8.95, 208.16 +/- 6.75 and 211.46 +/- 8.05 respectively; and the activity of MMP-2 of 24 h, 48 h and 72 h group was: 190.33 +/- 5.86, 214.33 +/- 8.39 and 212.67 +/- 11.59 respectively. (2) SB203580 significantly inhibited the TGF-beta(1)-induced expression of type I collagen mRNA, protein and MMP-2 activity (inhibition ratio: 51%, 24% and 20%); (3) PD98059 also significantly attenuated the TGF-beta(1)-induced expression of type I collagen mRNA, protein and MMP-2 activity (inhibition ratio: 42%, 13% and 16%).
CONCLUSIONTGF-beta(1) is capable of inducing the expression of type I collagen mRNA and protein and up-regulating MMP-2 activity in HLF-02 cells. p38 and ERK kinase signaling pathways play important role in regulation and control for this process.
