Effects of SHP2 regulating macrophage phenotypic transformation on fibrotic lesions in systemic scleroderma
Objective To investigate the effect of Src homology 2 domain-containing protein tyrosine phosphatase(SHP2)on inflammatory response and fibrosis in mice with systemic scleroderma(SSc)and its mechanism.Methods Forty mice were randomly divided into blank group,model group and experimental-L,-H groups,with 10 mice in each group.Except the blank group,the othier three groups of mice were established SSc model.The experimental-L,-H groups were given PHPS1 treatment of 2.5 mg·kg-1 and 5 mg·kg-1,respectively;blank group and model group were intraperitoneally injected with 0.9％NaCl.Four groups of mice were given the drug once a day for 20 days.Immunofluorescence staining was used to detect the macrophage infiltration.Flow cytometry was used to determine the macrophage polarization,real-time quantitative fluorescence polymerase chain reaction was used to detect the expression of M1 macrophage markers tumor necrosis factor-α(TNF-α),inducible nitric oxide synthase(iNOS)and M2 macrophage markers recombinant human arginase 1(Arg-1),transforming growth factor-β(TGF-β)in skin tissues and lung tissues.Results The proportions of M1-type macrophages labeled F4/80+CD86+in peripheral blood of experimental-H group,model group,blank group were(16.81±1.59)％,(36.95±3.54)％,(1.70±0.15)％,respectively;the proportions of M2-type macrophages labeled F4/80+CD206+were(18.49±1.76)％,(2.99±0.27)％,(16.62±1.49)％,respectively.The relative fluorescence intensity of F4/80 of macrophage marker in skin tissue were 1.46±0.13,2.14±0.19,1.00±0.04,respectively;TNF-α mRNA were 2.09±0.20,3.54±0.34,1.00±0.05,respectively;iNOS mRNA were 1.63±0.15,3.28±0.31,1.00±0.04,respectively,Arg-1 mRNA were 0.75±0.07,0.38±0.03,1.00±0.06,respectively,TGF-β mRNA were 0.79±0.08,0.41±0.04,1.00±0.04,respectively.In lung tissue,TNF-α mRNA were 1.46±0.14,2.61±0.25,1.00±0.04,respectively;iNOS mRNA were 1.53±0.15,2.82±0.29,1.00±0.03,respectively,Arg-1 mRNA were 0.67±0.07,0.31±0.03,1.00±0.05,respectively;TGF-β mRNA were 0.71±0.07,0.39±0.04,1.00±0.05,respectively.Compared with the model group,the above indexes in the experimental-H group had statistical significance(all P＜0.05).Conclusion The effect of SHP2 inhibitor on SSc mice can improve the inflammatory injury and fibrosis of skin and lung tissue,which is related to the regulation of macrophage polarization.
systemic sclerodermaSrc homology 2 domain-containing protein tyrosine phosphataseinflammationtissue fibrosismacrophages are polarizedlung injury
国家科技期刊平台
NSTL
万方数据
维普
