Receptor Activator of NF-κB Mediates Podocyte Injury in Diabetic Nephropathy

2021 ◽  
Author(s):  
Guibao Ke ◽  
Xueqin Chen ◽  
Ruyi Liao ◽  
Lixia Xu ◽  
Li Zhang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Podocyte Injury ◽  
Receptor Activator

scholarly journals Irbesartan Ameliorates Diabetic Nephropathy by Suppressing the RANKL-RANK-NF-κB Pathway in Type 2 Diabetic db/db Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xiao-Wen Chen ◽  
Xiao-Yan Du ◽  
Yu-Xian Wang ◽  
Jian-Cheng Wang ◽  
Wen-Ting Liu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Glomerular Sclerosis ◽  
Protective Effects ◽  
Podocyte Injury ◽  
Beneficial Effects ◽  
Focal Segmental Glomerular Sclerosis ◽  
Receptor Activator ◽  
Segmental Glomerular Sclerosis ◽  
Type 2 Diabetic

The receptor activator of NF-κB ligand (RANKL) and its receptor RANK are overexpressed in focal segmental glomerular sclerosis (FSGS), IgA nephropathy (IgAN), and membranous nephropathy (MN). However, the expression and the potential roles of RANKL and RANK in diabetic nephropathy (DN) remain unclear. Irbesartan (Irb) has beneficial effects against diabetes-induced renal damage, but its mechanisms are poorly understood. Our present study investigated the effects of Irb in DN and whether the renal protective effects of Irb are mediated by RANKL/RANK and the downstream NF-κB pathway in db/db mice. Our results showed that db/db mice revealed severe metabolic abnormalities, renal dysfunction, podocyte injury, and increased MCP-1; these symptoms were reversed by Irb. At the molecular level, RANKL and RANK were overexpressed in the kidneys of db/db mice and Irb downregulated RANKL and RANK and inhibited the downstream NF-κB pathway. Our study suggests that Irb can ameliorate DN by suppressing the RANKL-RANK-NF-κB pathway.

Circ_0000285 promotes podocyte injury through sponging miR-654-3p and activating MAPK6 in diabetic nephropathy

Gene ◽  
2020 ◽  
Vol 747 ◽  
pp. 144661 ◽  
Author(s):  
Tao Yao ◽  
Dongqing Zha ◽  
Chun Hu ◽  
Xiaoyan Wu
Keyword(s):  
Diabetic Nephropathy ◽  
Podocyte Injury

Protective effect of ferulic acid on STZ-induced diabetic nephropathy in rats

2020 ◽  
Vol 11 (4) ◽  
pp. 3706-3718 ◽  
Author(s):  
Min-you Qi ◽  
Xu-tao Wang ◽  
Hui-lin Xu ◽  
Zhang-liang Yang ◽  
Yin Cheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Protective Effect ◽  
Ferulic Acid ◽  
Podocyte Injury

Ferulic acid protects against diabetic nephropathy in STZ-induced rats by attenuating oxidative stress, inflammation, fibrosis and podocyte injury.

Gemigliptin improves renal function and attenuates podocyte injury in mice with diabetic nephropathy

2015 ◽  
Vol 761 ◽  
pp. 116-124 ◽  
Author(s):  
Eunsoo Jung ◽  
Junghyun Kim ◽  
Sung Ho Kim ◽  
Sanghwa Kim ◽  
Myung-Haing Cho
Keyword(s):  
Renal Function ◽  
Diabetic Nephropathy ◽  
Podocyte Injury

scholarly journals Renal Podocyte Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Junghyun Kim ◽  
Eunjin Shon ◽  
Chan-Sik Kim ◽  
Jin Sook Kim
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Glycated Haemoglobin ◽  
Protective Effects ◽  
Podocyte Injury ◽  
Podocyte Loss ◽  
Renal Changes ◽  
Hypoglycemic Drug ◽  
Antioxidant Effects

Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS), which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protective effects of metformin on the injury of renal podocytes in spontaneously diabetic Torii (SDT) rats, a new model for nonobese type 2 diabetes. Metformin (350 mg/kg/day) was given to SDT rats for 17 weeks. Blood glucose, glycated haemoglobin (HbA1c), and albuminuria were examined. Kidney histopathology, renal 8-hydroxydeoxyguanosine (8-OHdG) levels and apoptosis were examined. In 43-week-old SDT rats, severe hyperglycemia was developed, and albuminuria was markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, urinary and renal 8-OHdG levels were highly increased, and podocyte loss was shown through application of the TUNEL and synaptopodin staining. However, treatment of SDT rats with metformin restored all these renal changes. Our data suggested that diabetes-induced podocyte loss in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxidative injury.

scholarly journals Receptor Activator of NF-kappaB and Podocytes: Towards a Function of a Novel Receptor-Ligand Pair in the Survival Response of Podocyte Injury

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e41331 ◽  
Author(s):  
Shuangxin Liu ◽  
Wei Shi ◽  
Houqin Xiao ◽  
Xinling Liang ◽  
Chunyu Deng ◽  
...  
Keyword(s):  
Podocyte Injury ◽  
Receptor Ligand ◽  
Receptor Activator ◽  
Nf Kappab

Wnt signaling and podocyte dysfunction in diabetic nephropathy

2017 ◽  
Vol 65 (8) ◽  
pp. 1093-1101 ◽  
Author(s):  
Madhura Bose ◽  
Sadia Almas ◽  
Sharma Prabhakar
Keyword(s):  
Diabetes Mellitus ◽  
Renal Failure ◽  
Diabetic Nephropathy ◽  
Wnt Signaling ◽  
Therapeutic Strategies ◽  
Podocyte Injury ◽  
Functional Changes ◽  
Terminal Renal Failure ◽  
Cardiovascular Morbidity And Mortality

Nephropathy is a major microvascular complication of diabetes mellitus and often leads to terminal renal failure in addition to contributing significantly to cardiovascular morbidity and mortality. Despites continuous advances, the pathogenesis of diabetic nephropathy remains poorly understood. Recent studies have underscored the significance of structural and functional changes in podocytes in the development and progression of diabetic nephropathy. The role of podocytes in health and diabetic nephropathy and abnormalities including podocyte hypertrophy, effacement, and apoptosis, and a detailed discussion on the role played by the Wnt-β-catenin signaling pathway in podocyte injury and dysfunction are the focus of this review. In addition, the role played by Wnt signaling in mediating the effects of known therapeutic strategies for diabetic nephropathy is also discussed.

scholarly journals Automated image analysis of a glomerular injury marker desmin in spontaneously diabetic Torii rats treated with losartan

2014 ◽  
Vol 222 (1) ◽  
pp. 43-51 ◽  
Author(s):  
Tetsuhiro Kakimoto ◽  
Kinya Okada ◽  
Yoshihiro Hirohashi ◽  
Raissa Relator ◽  
Mizue Kawai ◽  
...  
Keyword(s):  
Image Analysis ◽  
Diabetic Nephropathy ◽  
Early Stage ◽  
Automated Image Analysis ◽  
Angiotensin Ii Receptor Blocker ◽  
Analysis Method ◽  
Glomerular Injury ◽  
Image Analysis Method ◽  
Podocyte Injury

Diabetic nephropathy is a major complication in diabetes and a leading cause of end-stage renal failure. Glomerular podocytes are functionally and structurally injured early in diabetic nephropathy. A non-obese type 2 diabetes model, the spontaneously diabetic Torii (SDT) rat, is of increasing preclinical interest because of its pathophysiological similarities to human type 2 diabetic complications including diabetic nephropathy. However, podocyte injury in SDT rat glomeruli and the effect of angiotensin II receptor blocker treatment in the early stage have not been reported in detail. Therefore, we have evaluated early stages of glomerular podocyte damage and the beneficial effect of early treatment with losartan in SDT rats using desmin as a sensitive podocyte injury marker. Moreover, we have developed an automated, computational glomerulus recognition method and illustrated its specific application for quantitatively studying glomerular desmin immunoreactivity. This state-of-the-art method enabled automatic recognition and quantification of glomerular desmin-positive areas, eliminating the need to laboriously trace glomerulus borders by hand. The image analysis method not only enabled assessment of a large number of glomeruli, but also clearly demonstrated that glomerular injury was more severe in the juxtamedullary region than in the superficial cortex region. This applied not only in SDT rat diabetic nephropathy but also in puromycin aminonucleoside-induced nephropathy, which was also studied. The proposed glomerulus image analysis method combined with desmin immunohistochemistry should facilitate evaluations in preclinical drug efficacy studies as well as elucidation of the pathophysiology of diabetic nephropathy.

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