Dapagliflozin reverses the imbalance of T helper 17 and T regulatory cells by inhibiting SGK1 in a mouse model of diabetic kidney disease.
Dapagliflozin reverses the imbalance of T helper 17 and T regulatory cells by inhibiting SGK1 in a mouse model of diabetic kidney disease.
复制标题
Dapagliflozin 通过抑制糖尿病肾病小鼠模型中的 SGK1 逆转 T 辅助细胞 17 和 T 调节细胞的不平衡
DOI：
10.1002/2211-5463.13147
复制
发表时间：
2021-05
期刊：
影响因子：
2.6
通讯作者：
Xue Y
中科院分区：
文献类型：
--
作者：
Wang D;Zhang Z;Si Z;Yang Y;Li S;Xue Y
辅助性T细胞17（Th 17）和调节性T细胞（Treg）亚群之间的失衡有助于糖尿病肾病（DKD）的发病机制。然而，导致这种不平衡的潜在监管机制尚不清楚。血清/糖皮质激素调节激酶1（SGK 1）已被认为以盐依赖性方式影响Th 17极化，钠/葡萄糖协同转运蛋白2抑制剂（SGLT 2 i）已被证明可调节肾小管中钠介导的转运。本研究旨在评价达格列净（Dap）对DKD的潜在获益，以及其对肾脏T细胞极化和相关细胞因子分泌的影响。我们用Dap或伏格列波糖（Vog）处理雄性db/db小鼠，并使用流式细胞术测量血液和肾脏中Th 17和Treg细胞的水平。我们发现糖尿病小鼠的Th 17细胞显著增加，而Treg细胞显著减少。此外，Dap通过抑制糖尿病肾脏中的SGK 1来抑制Th 17/Treg细胞的极化，并且这伴随着不依赖于血糖控制的白蛋白尿和肾小管间质纤维化的减轻。综上所述，这些结果表明Th 17/Treg细胞的失衡在DKD的进展中起重要作用。此外，Dap通过抑制SGK 1和逆转T细胞失衡来预防DKD。Th 17和Treg细胞亚群之间的失衡有助于糖尿病肾病的发病机制。我们发现糖尿病小鼠的Th 17细胞增加，而Treg细胞减少。达格列净通过抑制糖尿病肾脏中的SGK 1来抑制Th 17/Treg细胞的极化，这伴随着与血糖控制无关的白蛋白尿和肾小管间质纤维化的减轻。
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. An imbalance between Th17 and Treg cell subsets contributes to the pathogenesis of diabetic kidney disease. We found that Th17 cells were increased, while Treg cells were decreased in diabetic mice. Dapagliflozin 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.
登录
查看更多内容
DOI：
10.4049/jimmunol.1002615
发表时间：
2011-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jagannathan-Bogdan M;McDonnell ME;Shin H;Rehman Q;Hasturk H;Apovian CM;Nikolajczyk BS
通讯作者：
Nikolajczyk BS
影响因子：
16.2
作者：
Polidori D;Sha S;Mudaliar S;Ciaraldi TP;Ghosh A;Vaccaro N;Farrell K;Rothenberg P;Henry RR
通讯作者：
Henry RR
白质网络的整合与偏头痛患者心理介导的安慰剂反应的个体差异相关。
影响因子：
4.8
作者：
Liu, Jixin;Ma, Shaohui;Zhang, Ming
通讯作者：
Zhang, Ming
影响因子：
64.8
作者：
Wu, Chuan;Yosef, Nir;Thalhamer, Theresa;Zhu, Chen;Xiao, Sheng;Kishi, Yasuhiro;Regev, Aviv;Kuchroo, Vijay K.
通讯作者：
Kuchroo, Vijay K.
影响因子：
64.8
作者：
Kleinewietfeld, Markus;Manzel, Arndt;Titze, Jens;Kvakan, Heda;Yosef, Nir;Linker, Ralf A.;Muller, Dominik N.;Hafler, David A.
通讯作者：
Hafler, David A.