Effect Of FGF10 Monoclonal Antibodies On Expression Of SGK1,RORγt In Psoriasis Model

Psoriasis is a chronic and refractory disease.At present,it is believed that psoriasis patients are often accompanied by metabolic abnormalities.IL-17,IL-22,IL-23 and other cytokines in IL23/Th17 axis are involved in the occurrence of psoriasis.Serum and glucocorticoid-induced protein kinase-1(SGK1)and retinoic acid-related orphan receptor gamma t(ROR gamma t)play an important role in Th17 cell differentiation.At the same time,ROR gamma t reverse agonists can significantly alleviate psoriasis in animal models,but there is no report on the correlation between SGK1 and psoriasis at home and abroad.Imiquimod belongs to Toll-like receptor(TLR)7 and 8 agonists,which can produce erythema and scales on the surface of mouse skin after external application.Histologically,it can cause excessive proliferation of keratinocytes,new angiogenesis,inflammatory cell infiltration and so on.It has phenotypic and pathological characteristics similar to human psoriasis.Fibroblast growth factor lO(FGFlO)is secreted by fibroblasts and other mesenchymal-derived cells.It can effectively promote the proliferation,migration and differentiation of epithelial cells from various sources by the paracrine way of mesenchymal-epithelial interaction.Objective:To investigate the mechanism of anti-psoriasis treatment by detecting the changes of ROR gamma T and SGK1 in psoriasis lesions and normal skin around pigmented nevus and the changes of ROR gamma T and SGK1 in psoriasis-like lesions of imiquimod mice before and after treatment with monoclonal antibody to fibroblast growth factor 10.Methods:1.Collect 18 cases of psoriasis and 18 cases of pigmented nevus in pathological Department of dermatology,and detect the levels of SGK1 and ROR gamma t in normal skin around psoriasis and pigmented nevus.2.Eighteen female BABL/c mice were randomly divided into three groups,six mice in each group.The left back of the first group was set as blank control group and the right back was set as model group.The left and right back of the second group were treated with low and high concentration of monoclonal antibody against fibroblast growth factor 1O,respectively.The left back of the third group was treated with matrix and the right back was treated with hydrocortisone.The gross and histopathological changes of the lesions were observed.The pathological changes of psoriasis-like model were observed by HE staining and Baker score was performed under light microscope.The expression levels of SGK1 and ROR gamma t in skin tissue of mice in each group were detected by immunohistochemical method,and the differences among groups were evaluated by semi-quantitative scoring method.Result:1.The expressions of ROR gamma T and SGK1 in psoriasis patients were higher than those in normal skin around pigmented nevus(P < 0.05).2.Both low and high concentration of anti-fibroblast growth factor 10 monoclonal antibody treatment groups have therapeutic effects on imiquimod-induced psoriasis model.High dose anti-fibroblast growth factor 10 monoclonal antibody treatment group is better than low dose anti-fibroblast growth factor 10 treatment group,but less effective than hydrocortisone butyrate treatment group,the results are statistically significant(P < 0.05).3.The expression of SGK1 and ROR gamma t in imiquimod-induced psoriasis model was inhibited by high concentration of anti-fibroblast growth factor 10 monoclonal antibody(P < 0.003).The expression of ROR gamma t was inhibited by low concentration of anti-fibroblast growth factor 10 monoclonal antibody in imiquimod-induced psoriasis model(P < 0.003),but not SGK1(P > 0.003).Conclusion:1.ROR gamma T and SGK1 are involved in the pathogenesis of psoriasis.2.The anti-fibroblast growth factor 10 monoclonal antibody has a certain therapeutic effect on imiquimod-induced psoriasis-like mouse model.3.The monoclonal antibody against fibroblast growth factor 10 can inhibit the expression of ROR gamma T and SGK1 in imiquimod-induced psoriasis-like mice.