scholarly journals Interleukin-22 ameliorated renal injury and fibrosis in diabetic nephropathy through inhibition of NLRP3 inflammasome activation

2017 ◽  
Vol 8 (7) ◽  
pp. e2937-e2937 ◽  
Author(s):  
Shaofei Wang ◽  
Yubin Li ◽  
Jiajun Fan ◽  
Xuyao Zhang ◽  
Jingyun Luan ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Nlrp3 Inflammasome ◽  
Renal Injury ◽  
Inflammasome Activation ◽  
Interleukin 22 ◽  
Nlrp3 Inflammasome Activation

scholarly journals Mitochondria-Targeted Antioxidant Mito-Tempo Protects Against Aldosterone-Induced Renal Injury In Vivo

2017 ◽  
Vol 44 (2) ◽  
pp. 741-750 ◽  
Author(s):  
Wei Ding ◽  
Tingyan Liu ◽  
Xiao Bi ◽  
Zhiling Zhang
Keyword(s):  
Electron Microscopy ◽  
Renal Function ◽  
Nlrp3 Inflammasome ◽  
Renal Injury ◽  
Periodic Acid ◽  
Inflammasome Activation ◽  
Periodic Acid Schiff ◽  
Nlrp3 Inflammasome Activation

Background/Aims: Growing evidence suggests mitochondrial dysfunction (MtD) and the Nlrp3 inflammasome play critical roles in chronic kidney disease (CKD) progression. We previously reported that Aldosterone (Aldo)-induced renal injury in vitro is directly caused by mitochondrial reactive oxygen species (mtROS)-mediated activation of the Nlrp3 inflammasome. Here we aimed to determine whether a mitochondria-targeted antioxidant (Mito-Tempo) could prevent Aldo-induced kidney damage in vivo. Methods: C57BL/6J mice were treated with Aldo and/or Mito-Tempo (or ethanol as a control) for 4 weeks. Renal injury was evaluated by Periodic Acid-Schiff reagent or Masson’s trichrome staining and electron microscopy. ROS were measured by DCFDA fluorescence and ELISA. MtD was determined by real-time PCR and electron microscopy. Activation of the Nlrp3 inflammasome and endoplasmic reticulum stress (ERS) was detected via western blot. Results: Compared with control mice, Aldo-infused mice showed impaired renal function, increased mtROS production and MtD, Nlrp3 inflammasome activation, and elevated ERS. We showed administration of Mito-Tempo significantly improved renal function and MtD, and reduced Nlrp3 inflammasome activation and ERS in vivo. Conclusion: Mitochondria-targeted antioxidants may attenuate Aldo-infused renal injury by inhibiting MtD, the Nlrp3 inflammasome, and ERS in vivo. Therefore, targeting mtROS might be an effective strategy for preventing CKD.

scholarly journals Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy

2015 ◽  
Vol 87 (1) ◽  
pp. 74-84 ◽  
Author(s):  
Khurrum Shahzad ◽  
Fabian Bock ◽  
Wei Dong ◽  
Hongjie Wang ◽  
Stefan Kopf ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation

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 ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Nlrp3 Inflammasome ◽  
Protective Role ◽  
Tubular Damage ◽  
Inflammasome Activation ◽  
Compound C ◽  
Nlrp3 Inflammasome Activation ◽  
Amp Activated Protein Kinase ◽  
Relationship Of ◽  
The Relationship

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.

Targeting the NLRP3 Inflammasome in Diabetic Nephropathy

2021 ◽  
Vol 28 ◽  
Author(s):  
Ming Yang ◽  
Xi Wang ◽  
Yachun Han ◽  
Chenrui Li ◽  
Ling Wei ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
End Stage Renal Disease ◽  
Pathological Process ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Stage Renal Disease ◽  
End Stage ◽  
The Relationship

: 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.

scholarly journals Platelet Inhibition Prevents NLRP3 Inflammasome Activation and Sepsis-Induced Kidney Injury

2021 ◽  
Vol 22 (19) ◽  
pp. 10330
Author(s):  
Marivee Borges-Rodriguez ◽  
Corbin A. Shields ◽  
Olivia K. Travis ◽  
Robert W. Tramel ◽  
Cedar H. Baik ◽  
...  
Keyword(s):  
Renal Function ◽  
Platelet Activation ◽  
Nlrp3 Inflammasome ◽  
Renal Injury ◽  
Cecal Ligation ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Glomerular Injury ◽  
Activated Platelets ◽  
Nlrp3 Inflammasome Activation

Platelets, cellular mediators of thrombosis, are activated during sepsis and are increasingly recognized as mediators of the immune response. Platelet activation is significantly increased in sepsis patients compared to ICU control patients. Despite this correlation, the role of activated platelets in contributing to sepsis pathophysiology remains unclear. We previously demonstrated NOD-like receptor protein 3 inflammasome (NLRP3) inflammasome activation in sepsis-induced platelets from cecal-ligation puncture (CLP) rats. Activated platelets were associated with increased pulmonary edema and glomerular injury in CLP vs. SHAM controls. In this study, we investigated whether inhibition of platelet activation would attenuate NLRP3 activation and renal and pulmonary injury in response to CLP. CLP was performed in male and female Sprague Dawley (SD) rats (n = 10/group) to induce abdominal sepsis and SHAM rats served as controls. A subset of CLP animals was treated with Clopidogrel (10 mg/kg/day, CLP + CLOP) to inhibit platelet activation. At 72 h post-CLP, platelet activation and NLRP3 inflammasome assembly were evaluated, IL-1β and IL-18 were measured in plasma, and tissues, renal and pulmonary pathology, and renal function were assessed. Activated platelets were 7.8 ± 3.6% in Sham, 22 ± 6% in CLP and significantly decreased to 14.5 ± 0.6% in CLP + CLOP (n = 8–10/group, p < 0.05). NLRP3 inflammasome assembly was inhibited in platelets of CLP + CLOP animals vs. CLP. Significant increases in plasma and kidney IL-1β and IL-18 in response to CLP were decreased with Clopidogrel treatment. Renal injury, but not lung histology or renal function was improved in CLP + CLOP vs. CLP. These data provide evidence that activated platelets may contribute to sepsis-induced renal injury, possibly via NLRP3 activation in platelets. Platelets may be a therapeutic target to decrease renal injury in septic patients.

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