Research progress of tyrosine kinase inhibitors in the treatment of pulmonary fibrosis / 中国综合临床

Objective Pulmonary fibrosis is a progressive chronic lung disease with a high incidence.Although the path of the disease has not been fully elucidated,the pathogenesis of the disease is roughly similar.Tyrosine kinases are involved in a series of signaling pathways that are critical for cell homeostasis.Substantial evidence from in vitro studies and experimental animal models suggests that tyrosine kinases play a role in promoting the development and progression of pulmonary fibrosis,and tyrosine kinase inhibitors have shown good anti-fibrosis and anti-inflammatory effect in animal models of pulmonary fibrosis.

Effect of nilotinib on silicon dioxide-induced proliferation and collagen synthesis in HFL-1 cells / 中国职业医学

OBJECTIVE: To observe the effects of nilotinib on silicon dioxide(SiO_2)-induced cell proliferation and collagen synthesis in human fetal lung fibroblast-1(HFL-1) cells and to explore the related mechanism. METHODS: ⅰ) HFL-1 cells were induced with different doses of SiO_2 suspension(0, 5,10, 25, 50 and 100 mg/L) for 24.0 hours. The expression of transforming growth factor-β1(TGF-β1), C-Abl, and platelet-derived growth factor receptor(PDGFR) was detected by Western blot, and the dose of SiO_2 in subsequent experiments was screened. ⅱ) HFL-1 cells were randomly divided into 6 groups: 1) the control group: no treatment; 2) the solvent control group: cells were treated with 0.10% dimethyl sulfoxide; 3) the SiO_2 stimulation group: cells were induced with SiO_2 suspension at a dose of 50 mg/L for 24.0 hours; 4)-6) the nilotinib groups: cells were induced with SiO_2 suspension at a dose of 50 mg/L for 24.0 hours and treated with nilotinib at the concentration of 5, 10, or 15 mmol/L for 24.0 hours. Cell proliferation was detected by MTS assay. The TGF-β1 protein secreted by cells was measured using enzyme linked immunosorbent assay. The expression of TGF-β1, C-Abl, platelet derived growth factor(PDGF), PDGFR and collagen typeⅠproteins was measured by Western blot. RESULTS: ⅰ) The dose of the SiO_2 in the experiments was set to 50 mg/L. ⅱ) The cell proliferation rate of HFL-1 cells in the SiO_2 stimulation group and the 3 nilotinib groups was higher than that in control group and solvent control group(P<0.05). The proliferation rates of HFL-1 cells in 10 and 15 mmol/L nilotinib groups were lower than that in SiO_2 stimulation group(P<0.05). The level of TGF-β1 and the protein relative expression levels of TGF-β1, collagen typeⅠ, C-Abl, PDGFR and PDGF in HFL-1 cells of SiO_2 stimulation group were higher than those in control group and solvent control group(P<0.05). The above indexes of HFL-1 cells in 15 mmol/L nilotinib group were lower than that in SiO_2 stimulation group(P<0.05); the above indexes of HFL-1 cells in 5 mmol/L nilotinib group were not significantly different from those in SiO_2 stimulation group(P>0.05). The level of TGF-β1 and the relative expression level of C-Abl protein in HFL-1 cells of 10 mmol/L nilotinib group were lower than those in SiO_2 stimulation group(P<0.05). CONCLUSION: Nilotinib can inhibit the proliferation of HFL-1 cells and reduce the expression of collagen typeⅠprotein induced by SiO_2. This process may be achieved by inhibiting tyrosine kinase-mediated signaling pathway.