Transforming growth factor-beta1 induced phenotypic differentiation of human lung fibroblasts through mitogen activated protein kinase-dependent pathway.
- Author:
Yong-bin HU
1
;
De-yun FENG
;
Jin-wu PENG
;
Ling CHU
;
Zhi LIN
;
Qing-fu ZENG
Author Information
- Publication Type:Journal Article
- MeSH: Actins; biosynthesis; genetics; Cell Line; Extracellular Signal-Regulated MAP Kinases; antagonists & inhibitors; metabolism; Fibroblasts; drug effects; metabolism; Flavonoids; pharmacology; Humans; Imidazoles; pharmacology; Lung; cytology; Phenotype; Phosphorylation; Pyridines; pharmacology; RNA, Messenger; genetics; Transforming Growth Factor beta1; pharmacology; p38 Mitogen-Activated Protein Kinases; antagonists & inhibitors; metabolism
- From: Chinese Journal of Industrial Hygiene and Occupational Diseases 2005;23(2):109-112
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the role of MAPK signal transduction in TGF-beta1 induced phenotypic differentiation of human lung fibroblasts.
METHODHuman lung fibroblasts cell line (HLF-02) were cultured and then stimulated with 10 ng/ml TGF-beta1 for different time; SB203580 or PD98059 was added into culture medium to prevent p38 or Erk kinase pathway before incubating with TGF-beta1; the expression of alpha-smooth muscle actin (alpha-SMA) was detected by Western blotting and RT-PCR; Western blotting was used to assay phosphorylation of p38, Erk, and JNK kinase.
RESULTS(1) In the process of stimulation by TGF-beta1, the alpha-SMA mRNA expression levels of 24, 48 and 72 h groups were 1.87 +/- 0.11, 2.49 +/- 0.10, 3.02 +/- 0.15 respectively; and the alpha-SMA protein expression levels of 24, 48 and 72 h groups were 3.20 +/- 0.14, 3.96 +/- 0.21, 4.57 +/- 0.13 respectively. (2) TGF-beta1 induced p38, Erk kinase phosphorylation but not JNK kinase. (3) The inhibitors SB203580 and PD98059 suppressed TGF-beta1-induced p38 kinase and Erk phosphorylation respectively. (4) SB203580 significantly attenuated TGF-beta1-induced alpha-SMA mRNA and protein expression (inhibition rate: 30% and 40%); PD98059 also significantly inhibited TGF-beta1-induced alpha-SMA mRNA and protein expression (inhibition rate: 10% and 20%).
CONCLUSIONTGF-beta1 is capable of inducing the phenotypic differentiation of HLF-02, which is regulated by p38 and Erk kinase signal pathway.
