Study on the effects of artemisinin in improving imiquimod-induced psoriasis-like mice
Objective To investigate the effect of artemisinin on signal transducer and activator of transcription 3(STAT3)signalling pathway in psoriasis-like mice through modulation of microRNA-129-5p(miRNA-129-5p)/calcium/calmodulin-dependent protein kinase N(CaMK4)axis-mediated signal transduction and activator of transcription factor 3(STAT3)signalling pathway in psoriasis-like mice.Methods All mice were randomly divided into control group(normal feeding),model group(0.9%NaCl),positive control group(1 mg·kg-1 methotrexate),experimental group(100 g·mL-1 artemisinin),miR-129-5p inhibitor group(miR-129-5p inhibitor was injected into the tail vein on the basis of the experimental group),siCaMK4 group(siCaMK4 was injected into the tail vein on the basis of the experimental group).Except for the control group,the mice in each group were treated with imiquimod to construct a psoriasis model.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect miR-129-5p and CaMK4 mRNA relative expression;dual luciferase reporter gene assay was used to verify the targeting of miR-129-5p and CaMK4.Psoriasis area and severity index(PASI)were used to assess skin lesions;enzyme-linked immunosorbent assay(ELISA)was used to detect interleukin-17(IL-17),IL-23,IL-22 levels;Western blot were used to detect the STAT3 pathway protein expression.Results The miR-129-5p relative expression levels were 1.00±0.18,0.54±0.07,0.88±0.13;CaMK4 mRNA relative expression levels were 1.00±0.17,1.68±0.31,1.20±0.22 in the control,model,and experimental groups,respectively.The 7 th day PASIs of the control,model,positive control,experimental,miR-129-5p inhibitor group,and siCaMK4 group were 0,(10.20±1.22),(7.20±0.68),(6.30±0.66),(7.50±0.88),and(4.80±0.63)scores,respectively;the expression levels of IL-17 were(1.89±0.19),(3.56±0.38),(2.22±0.28),(2.55±0.33),(3.19±0.41),(1.99±0.22)pg·mL-1,respectively;IL-23 expression levels were(4.48±0.61),(6.28±0.77),(5.22±0.51),(5.33±0.61),(6.01±0.66),(4.64±0.55)pg·mL-1,respectively;IL-22 expression levels were(5.14±0.68),(7.84±0.87),(5.86±0.66),(5.99±0.62),(6.88±0.73),(5.22±0.60)pg·mL-1,respectively;p-STAT3/STAT3 protein ratios were 0.38±0.04,0.68±0.07,0.45±0.05,0.48±0.05,0.57±0.07,and 0.42±0.04,respectively;compared the model group with the control group,compared the positive control group,the experimental group with the model group,and compared the miR-129-5p inhibitor group,siCaMK4 group with the experimental group,the differences were statistically significant(P<0.05,P<0.01,P<0.001).Conclusion Artemisinin improves skin lesion status and inhibits inflammatory response in psoriasis mice,which may be related to the modulation of miR-129-5p/CaMK4 axis mediating STAT3 signalling pathway.
artemisininpsoriasismicroRNA-129-5pcalcium/calmodulin-dependent protein kinase Ⅳsignal transducer and activator of transcription 3