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

2021 ◽  
Vol 12 ◽  
Author(s):  
Ming Yang ◽  
Shilu Luo ◽  
Na Jiang ◽  
Xi Wang ◽  
Yachun Han ◽  
...  

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.

2021 ◽  
Vol 28 ◽  
Author(s):  
Ming Yang ◽  
Xi Wang ◽  
Yachun Han ◽  
Chenrui Li ◽  
Ling Wei ◽  
...  

: Diabetic nephropathy (DN) is one of the most common complications of diabetes and the main cause of end-stage renal disease (ESRD). The inflammatory response plays a key role in the pathological process of DN. As the most deeply studied inflammasome, NLRP3 should not be overlooked in DN. Its abnormal activation accelerates DN progression. In this review, we summarize our understanding of the structural composition and activation factors of the NLRP3 inflammasome. Moreover, the relationship between NLRP3 inflammasome activation, and the potential of the NLRP3 inflammasome as a therapeutic target for DN will also be discussed.


2015 ◽  
Vol 87 (1) ◽  
pp. 74-84 ◽  
Author(s):  
Khurrum Shahzad ◽  
Fabian Bock ◽  
Wei Dong ◽  
Hongjie Wang ◽  
Stefan Kopf ◽  
...  

2020 ◽  
Author(s):  
Fengxia Guo ◽  
Bing Hu ◽  
Yanhua Sha ◽  
Kangning Zhu ◽  
Gang Li

Abstract BackgroundIncreasing evidence suggests that transcription factor EB (TFEB) inhibits inflammation in endothelial cell (ECs) and reduces development of atherosclerosis. However, little is known about the mechanism of action of TFEB on inflammation in atherosclerosis (AS).MethodsThe levels of TFEB, NLRP3, VCAM-1, ICAM-1, E-selectin, MCP-1, cleaved caspase-1, IL-1β and IL-18 in ECs were examined by immunoblotting, quantitative real time-polymerase chain reaction (qRT-PCR) , Enzyme-linked immunosorbent assay. The LDH activity were examined by LDH assay. TUNEL-positive cell were examined by TUNEL assay. The relationship between TFEB and NLRP3 were examined by immunofluorescence and coimmunoprecipitation. The effects of TFEB on atherosclerotic lesions by hematoxylin and eosin, TUNEL and collagen staining in the aortic valve of ApoE-/- mice fed a high fat diet (HFD).ResultsHere, we report that H2O2-induced cell pyroptosis and inflammatory response were mainly due to nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation. The nuclear protein TFEB was significantly increased by H2O2, and knockdown of TFEB aggravated cell pyroptosis and inflammatory response. TFEB directly bound to NLRP3 and blocked NLRP3-mediated cell pyroptosis and inflammatory response. The effect of H2O2 on TFEB might be associated with AMP-activated protein kinase/mechanistic target of rapamycin-dependent signaling pathways.ConclusionsOur findings indicated that a novel TFEB–NLRP3 axis was a critical regulator in EC pyroptosis and inflammation, which could be potential therapeutic targets in AS and related cardiovascular diseases.


2013 ◽  
Vol 45 (5) ◽  
pp. 932-943 ◽  
Author(s):  
Kehong Chen ◽  
Jianguo Zhang ◽  
Weiwei Zhang ◽  
Jinhua Zhang ◽  
Jurong Yang ◽  
...  

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