[p38/ERK signal pathways regulating the expression of type I collagen and activity of MMP-2 in TGF-beta1-stimulated HLF-02 cells].

Objective To investigate the role of TGFβ_1/MAPK signaling pathways in the expression of typeⅠcollagen and activity of MMP-2,9 in human lung fibroblasts. Methods Human lung fibroblasts cell line(HLF-02) was cultured and and then stimulated with 10 ng/ml TGF-β_1 for different time;SB203580 or PD98059 was added into culture medium to block p38 or ERK kinase pathway before incubated with TGF-β_1;the expression of typeⅠ collagen was detected by Westerm 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-β_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 respectivley;and the typeⅠcollagen 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,48h 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-β_1-induced expression of typeⅠcollagen mRNA,protein and MMP-2 activity(inhibition ratio:51%,24% and 20%);(3)PD98059 also significantly attenuated the TGF-β_1-induced expression of typeⅠcollagen mRNA,protein and MMP-2 activity(inhibition ratio:42%,13% and 16%). Conclusion TGF-β_1 is capable of inducing the expression of typeⅠcollagen 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.