Open AccessDapagliflozin reverses the imbalance of T helper 17 and T regulatory cells by inhibiting SGK1 in a mouse model of diabetic kidney disease
Author(s) -
Wang Dan,
Zhang Zikun,
Si Zekun,
Yang Yanlin,
Li Shuangshuang,
Xue Yaoming
Publication year - 2021
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.13147
Subject(s) - sgk1 , medicine , dapagliflozin , pathogenesis , endocrinology , albuminuria , kidney , flow cytometry , epithelial sodium channel , diabetes mellitus , glucocorticoid , cancer research , immunology , type 2 diabetes , chemistry , sodium , organic chemistry
An imbalance between T helper 17 (Th17) and T regulatory (Treg) cell subsets contributes to the pathogenesis of diabetic kidney disease (DKD). However, the underlying regulatory mechanisms that cause this imbalance are unknown. Serum/glucocorticoid‐regulated kinase 1 (SGK1) has been suggested to affect Th17 polarization in a salt‐dependent manner, and sodium/glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to regulate sodium‐mediated transportation in the renal tubules. This study aimed to evaluate the potential benefits of dapagliflozin (Dap) on DKD, as well as its influence on shifting renal T‐cell polarization and related cytokine secretion. We treated male db/db mice with Dap or voglibose (Vog) and measured blood and kidney levels of Th17 and Treg cells using flow cytometry. We found that Th17 cells were significantly increased, while Treg cells were significantly decreased in diabetic mice. Moreover, Dap suppressed the polarization of Th17/Treg cells by inhibiting SGK1 in diabetic kidneys, and this was accompanied by attenuation of albuminuria and tubulointerstitial fibrosis independent of glycemic control. Taken together, these results demonstrate that the imbalance of Th17/Treg cells plays an important role in the progression of DKD. Moreover, Dap protects against DKD by inhibiting SGK1 and reversing the T‐cell imbalance.