Transforming growth factor-beta1 induced phenotypic differentiation of human lung fibroblasts through mitogen activated protein kinase-dependent pathway / 中华劳动卫生职业病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the role of MAPK signal transduction in TGF-beta1 induced phenotypic differentiation of human lung fibroblasts.</p><p><b>METHOD</b>Human 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.</p><p><b>RESULTS</b>(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%).</p><p><b>CONCLUSION</b>TGF-beta1 is capable of inducing the phenotypic differentiation of HLF-02, which is regulated by p38 and Erk kinase signal pathway.</p>