Exploring the mechanism of S100A8 in coal dust-induced pulmonary fibrosis based on the RAGE/NF-κB signaling axis
Objective To observe the toxic effects of coal dust at different concentrations on the lungs of mice and explore the mechanism by which S100 calcium binding protein A8(S100A8)promotes lung fibrosis in coal mouse pneumoconiosis(CMP)through the receptor for advanced glycation end products(RAGE)/NF-κB signaling axis.Methods A CMP model was established,and C57BL/6 mice were randomly divided into four groups:saline group(50 μ L,NS),low-concentration coal dust group(50 μL,10 mg/mL,CMP-Low),medi-um-concentration coal dust group(50 μL,30 mg/mL,CMP-Medium),and high-concentration coal dust group(50 μL,50 mg/mL,CMP-High).Mice were intranasally instilled twice a week for one month.Mouse body weight and respiratory parameters of lung function were measured to observe the effects of different concentra-tions of coal dust on body weight changes and lung function.HE,Masson,and Sirius Red staining experiments were conducted to detect the effects of different concentrations of coal dust on lung inflammation and fibrosis in mice.IHC staining experiment was conducted to observe the effects of coal dust at different concentrations on the protein expression level of S100A8.Western Blot experiments were used to detect the protein expression levels of S100A8,RAGE,NF-κB,α-SMA,Fibronectin,and TGF-β1 in the lung tissues of mice at different concentrations of coal dust.Results Compared with the NS group,the body weight and lung function of mice in the CMP-Medium and CMP-High groups decreased significantly,while there was no statistically signif-icant difference between the CMP-Low group and the NS group(P＞0.05).Compared with the NS group,the CMP-Medium and CMP-High groups promoted the progression of inflammation and fibrosis with statisti-cally significant differences(P＜0.01).Compared with the NS group,the protein expression levels of S100A8,RAGE,NF-κB,α-SMA,Fibronectin,and TGF-β1 were upregulated in the lung tissues of the CMP-Medium and CMP-High groups(P＜0.05).Conclusion The higher the concentration of coal dust,the greater the toxic effect on the lungs of mice.The expression level of S100A8 protein is upregulated in CMP,and S100A8 promotes coal dust-induced pulmonary fibrosis through the RAGE/NF-κB signaling axis.
pneumoconiosispulmonary fibrosisS100 calcium-binding protein A8advanced glycation end products receptor
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维普
