SGK1 Mediates Treg/th17 Imbalance And Target Organ Inflammation In Angiotensin Ⅱ-induced Hypertension

It has been demonstrated that serum/glucocorticoid regulated kinase 1(SGK1)plays a critical role in the regulation of regulatory T cells/T helper 17 cells(Treg/Th17)balance by promoting Th17 differentiation and inhibiting Treg differentiation.In the present study,we hypothesized that SGK1 is involved in Th17/Treg imbalance and target organ damage in Angiotensin II(AngⅡ)-induced hypertensive mice.Results show that SGK1 inhibitor EMD638683 significantly reversed cardiac dysfunction in echocardiography and renal dysfunction as indicated by decreased serum creatinine and blood urine nitrogen in AngⅡ-infused mice.Flowcytometric assay shows that there was significant splenic Th17/Treg imbalance as indicated by the increased Th17 cells(CD4~+-IL17A~+cells)and decreased Treg cells(CD4~+-Foxp3~+).Meanwhile,SGK1 was increased as indicated by the increased m RNA and protein level in spleen.Notably,flowcytometric assay and real-time PCR show that this Th17/Treg imbalance and increased SGK1 expression were also present in lymphocytes isolated from both kidney and heart.Furthermore,real-time PCR study shows that Th17-related cytokines including IL-17A,IL-23 and tumor necrosis factor?(TNF-?)were increased and Treg-related cytokine IL-10 was decreased in lymphocytes isolated from kidney and heart in AngⅡ-infused mice.Notably,all changes were significantly inhibited by the treatment of EMD638683.Finally,EMD638683significantly prevented the increase of serum pro-inflammatory cytokines including IL-17,IL-23 and TNF-?,and the decrease of serum anti-inflammatory cytokine IL-10 in enzyme-linked immunosorbent assay.These results suggest that SGK1 was involved in Th17/Treg imbalance and target organ damage in AngⅡ-induced hypertension.