DsbA-L Ameliorates Renal Injury Through the AMPK/NLRP3 Inflammasome Signaling Pathway in Diabetic Nephropathy

Frontiers in Physiology

Yan Liu¹  Chanyue Zhao¹  Ming Yang¹  Xiaofen Xiong¹  Shilu Luo¹  Lin Sun¹  Na Jiang¹  Yachun Han¹  Hao Zhao¹  Xuejing Zhu¹  Xi Wang² 

[1] Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital, Central South University, Changsha, China;Department of Nutrition, Xiangya Hospital, Central South University, Changsha, China;

关键词: NLRP3 inflammasome;    DsbA-L;    AMPK;    diabetic nephropathy;    inflammation;   

DOI  :  10.3389/fphys.2021.659751

来源: DOAJ

【 摘 要 】

NLRP3-mediated inflammation is closely related to the pathological progression of diabetic nephropathy (DN). DsbA-L, an antioxidant enzyme, plays a protective role in a variety of diseases by inhibiting ER stress and regulating metabolism. However, the relationship of DsbA-L with inflammation, especially the NLRP3 inflammasome, has not been examined. In this study, we note that activation of the NLRP3 inflammasome and exacerbated fibrosis were observed in the kidneys of diabetic DsbA-L-knockout mice and were accompanied by decreased phosphorylation of AMP-activated protein kinase (AMPK). Moreover, correlation analysis shows that the phosphorylation of AMPK was negatively correlated with NLRP3 expression and tubular damage. In addition, the decreased AMPK phosphorylation and NLRP3 activation induced by high glucose (HG) in HK-2 cells could be alleviated by the overexpression of DsbA-L. Interestingly, the protective effect of DsbA-L was eliminated after treatment with compound C, a well-known AMPK inhibitor. Our findings suggest that DsbA-L inhibits NLRP3 inflammasome activation by promoting the phosphorylation of AMPK.

【 授权许可】

Unknown