The Role Of SGK1 In The Pathogenesis Of Psoriasis

【Objective】To investigate the role of SGK1 in the pathogenesis of psoriasis and provide a new possible therapeutic target.【Methods】1.The blood of the psoriatic patients and healthy adults were collected,the expression level of SGK1 was measured through flow cytometry.2.The effect of SGK1 inhibition on psoriatic inflammation induced by imiquimod was evaluated in the primary macrophages derived from peripheral blood of people and RAW264.7 cell line.3.The Balb/c mice were injected with SGK1 inhibitor EMD638683 in the intraperitoneal continuously for 10 days and applied with imiquimod cream or physiological saline on the back skin of mice for 7 days.All mice were sacrificed on day 11 and the back lesions and peripheral blood of the mice were collected.4.The expression of SGK1 and related inflammatory factors were evaluated through flow cytometry,q RT-PCR,western blot and ELISA.5.Enumeration data were compared by chi-square tests,the independent two-samples t-test was used for the comparison of means between the two groups,and analysis of variance(ANOVA)was used for comparing means within multiple groups.【Results】1.The expression of SGK1 in the macrophages derived from peripheral blood of psoriatic patients is significantly lower than healthy adults.2.Inhibition of SGK1 enhanced the psoriatic inflammation induced by imiquimod in RAW264.7 cells.The primary macrophage derived from peripheral blood of patients with psoriasis showed a more activated inflammatory signaling pathway induced by imiquimod than healthy adults.3.After the intraperitoneal injection of EMD638683 inhibitor,psoriatic inflammation on the back skin of the Balb/c mice was increased compared with the control group(normal saline solution),and the secret of pro-inflammatory cytokines in the skin lesions was also augmented.【Conclusion】SGK1 is a potent negative regulator of IMQ-induced psoriatic inflammatory signaling pathway.