scholarly journals Complement C5a Induces Renal Injury in Diabetic Kidney Disease by Disrupting Mitochondrial Metabolic Agility

Diabetes ◽  
2019 ◽  
Vol 69 (1) ◽  
pp. 83-98 ◽  
Author(s):  
Sih Min Tan ◽  
Mark Ziemann ◽  
Vicki Thallas-Bonke ◽  
Matthew Snelson ◽  
Vinod Kumar ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Renal Injury ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Complement C5a

scholarly journals Urinary Periostin as an Early Predictor of Renal Injury in Diabetic Kidney Disease: A Tertiary Centre Experience

2019 ◽  
Vol 9 (3) ◽  
pp. 100-104
Author(s):  
Munna Lal Patel ◽  
Rekha Sachan ◽  
Durgesh Pushkar ◽  
Shyam Chand Chaudhary ◽  
Kamlesh Kumar Gupta
Keyword(s):  
Kidney Disease ◽  
Renal Injury ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Tertiary Centre ◽  
Early Predictor

Targeted deletion of NADPH-Oxidase Nox4 from proximal tubules is dispensable for diabetic kidney disease development

2020 ◽  
Author(s):  
Vicki Thallas-Bonke ◽  
Sih Min Tan ◽  
Runa S Lindblom ◽  
Matthew Snelson ◽  
Cesare Granata ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Nadph Oxidase ◽  
Renal Injury ◽  
Renal Fibrosis ◽  
Diabetic Kidney Disease ◽  
Proximal Tubules ◽  
Disease Development ◽  
Diabetic Kidney ◽  
Genetic Ablation ◽  
Proximal Tubular

Abstract Background The NADPH oxidase isoform, Nox4, mediates reactive oxygen species (ROS) production and renal fibrosis in diabetic kidney disease at the level of the podocyte. However, the mitochondrial localization of Nox4 and its role as a mitochondrial bioenergetic sensor has recently been reported. Whether Nox4 drives pathology in diabetic kidney disease within the proximal tubular compartment, which is densely packed with mitochondria, is not yet known. Methods We generated a proximal tubular specific Nox4 knockout mouse model by breeding Nox4flox/flox mice with mice expressing Cre recombinase under the control of the Sglt2 promoter. Subsets of Nox4ptKO mice and their Nox4flox/flox littermates were injected with streptozotocin (STZ) to induce diabetes. Mice were followed for 20 weeks and renal injury was assessed. Results Genetic ablation of proximal tubular Nox4 (Nox4ptKO) resulted in no change in renal function and histology. Nox4ptKO mice and Nox4flox/flox littermates injected with STZ exhibited the hallmarks of diabetic kidney disease including hyperfiltration, albuminuria, renal fibrosis and glomerulosclerosis. Surprisingly, diabetes-induced renal injury was not improved in Nox4ptKOSTZ mice compared to Nox4flox/flox STZ mice. Although diabetes conferred ROS overproduction and increased mitochondrial oxygen consumption rate, proximal tubular deletion of Nox4 did not normalize oxidative stress or mitochondrial bioenergetics. Conclusion Taken together, these results demonstrate that genetic deletion of Nox4 from the proximal tubules does not influence diabetic kidney disease development, indicating that Nox4 localization within this highly energetic compartment is dispensable for chronic kidney disease pathogenesis in the setting of diabetes.

scholarly journals General Control of Amino Acid Synthesis 5-Like 1-Mediated Acetylation of Manganese Superoxide Dismutase Regulates Oxidative Stress in Diabetic Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Tingting Lv ◽  
Yao Lu ◽  
Yi Liu ◽  
Hong Feng ◽  
Chensheng Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Renal Injury ◽  
Manganese Superoxide Dismutase ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Redox Homeostasis ◽  
Acid Synthesis ◽  
Amino Acid Synthesis ◽  
Diabetic Kidney

Diabetic kidney disease (DKD) is the major cause of end-stage renal disease (ESRD). In the past few decades, there has been a large amount of evidence to highlight the pivotal role of oxidative stress in the development and progression of DKD. However, the detailed molecular mechanisms are not fully elucidated. A new sight has been established that the mitochondrial acetyltransferase GCN5L1 participates in cellular redox homeostasis maintenance in DKD. Firstly, we found that the expression of GCN5L1 is significantly elevated both in human and mouse kidney tissues with DKD and in hyperglycemic renal tubular epithelial cells (TECs), while deletion of GCN5L1 could effectively ameliorate oxidative stress-induced renal injury in DKD. Furthermore, deletion of GCN5L1 could reduce MnSOD acetylation on lysine 68 and activate its activity, thereby scavenging excessive ROS and relieving oxidative stress-induced renal inflammation and fibrosis. In general, GCN5L1-mediated acetylation of MnSOD exacerbated oxidative stress-induced renal injury, suggesting that GCN5L1 might be a potential intervention target in DKD.

scholarly journals Monocyte/macrophage chemokine receptor CCR2 mediates diabetic renal injury

2011 ◽  
Vol 301 (6) ◽  
pp. F1358-F1366 ◽  
Author(s):  
Alaa S. Awad ◽  
Gilbert R. Kinsey ◽  
Konstantine Khutsishvili ◽  
Ting Gao ◽  
W. Kline Bolton ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Chemokine Receptor ◽  
Renal Injury ◽  
Diabetic Kidney Disease ◽  
Renal Tissue ◽  
Direct Role ◽  
Diabetic Kidney ◽  
Glucose Levels ◽  
Macrophage Recruitment ◽  
Monocyte Migration

Monocyte/macrophage recruitment correlates strongly with the progression of renal impairment in diabetic nephropathy (DN). C-C chemokine receptor (CCR)2 regulates monocyte/macrophage migration into injured tissues. However, the direct role of CCR2-mediated monocyte/macrophage recruitment in diabetic kidney disease remains unclear. We report that pharmacological blockade or genetic deficiency of CCR2 confers kidney protection in Ins2Akita and streptozotocin (STZ)-induced diabetic kidney disease. Blocking CCR2 using the selective CCR2 antagonist RS504393 for 12 wk in Ins2Akita mice significantly attenuated albuminuria, the increase in blood urea nitrogen and plasma creatinine, histological changes, and glomerular macrophage recruitment compared with vehicle. Furthermore, mice lacking CCR2 (CCR2−/−) mimicked CCR2 blockade by reducing albuminuria and displaying less fibronectin mRNA expression and inflammatory cytokine production compared with CCR2+/+ mice, despite comparable blood glucose levels. Bone marrow-derived monocytes from CCR2+/+ or CCR2−/− mice adoptively transferred into CCR2−/− mice reversed the renal tissue-protective effect in diabetic CCR2−/− mice as evaluated by increased urinary albumin excretion and kidney macrophage recruitment, indicating that CCR2 is not required for monocyte migration from the circulation into diabetic kidneys. These findings provide evidence that CCR2 is necessary for monocyte/macrophage-induced diabetic renal injury and suggest that blocking CCR2 could be a novel therapeutic approach in the treatment of DN.

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