A20 overexpression exerts protective effects on podocyte injury in lupus nephritis by downregulating UCH‐L1

2019 ◽  
Vol 234 (9) ◽  
pp. 16191-16204 ◽  
Author(s):  
Ling Sun ◽  
Lu‐Xi Zou ◽  
Yu‐Chen Han ◽  
Ling Wu ◽  
Ting Chen ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Protective Effects ◽  
Podocyte Injury

scholarly journals Protective effects of DPP-4 inhibitor on podocyte injury in glomerular diseases

2020 ◽  
Author(s):  
Ayano Kubo ◽  
Teruo Hidaka ◽  
Maiko Nakayama ◽  
Yu Sasaki ◽  
Miyuki Takagi ◽  
...  
Keyword(s):  
Proximal Tubules ◽  
Pleiotropic Effects ◽  
Protective Effects ◽  
Crescent Formation ◽  
Glomerular Diseases ◽  
Podocyte Injury ◽  
Dipeptidyl Peptidase 4 ◽  
Anti Oxidant ◽  
Glucagon Like Peptide 1 ◽  
Antigen Antibody

Abstract Background Dipeptidyl peptidase-4 (DPP-4) is a serine protease that inhibits the degradation of glucagon-like peptide 1. DPP-4 inhibitors are used worldwide to treat type 2 diabetes mellitus and were recently shown to have pleiotropic effects such as anti-oxidant, anti-inflammatory, and anti-fibrotic actions. DPP-4 inhibitors improve albuminuria and renal injury including glomerular damage independent of its hypoglycemic effect. Although DPP-4 is mainly expressed in the kidney, the physiological function of DPP-4 remains unclear. Methods The localization of renal DPP-4 activity was determined in human renal biopsy specimens with glycyl-1-prolyl-4-methoxy-2-naphthylamide and the effects of a DPP-4 inhibitor were examined in human cultured podocyte. Results DPP-4 activity under normal conditions was observed in some Bowman's capsular epithelial cells and proximal tubules, but not in the glomerulus. DPP-4 activity was observed in crescent formation in anti-neutrophil myeloperoxidase cytoplasmic antigen antibody nephritis, nodular lesions in diabetic nephropathy, and some podocytes in focal segmental glomerulosclerosis. Notably, the DPP-4 inhibitor saxagliptin suppressed DPP-4 activity in podocytes and the proximal tubules. To assess the effect of DPP-4 inhibitor on podocytes, human cultured podocytes were injured by Adriamycin, which increased DPP-4 activity; this activity was dose-dependently suppressed by saxagliptin. Treatment with saxagliptin maintained the structure of synaptopodin and RhoA and improved the detachment of podocytes. Conclusions DPP-4 activity induces degradation of synaptopodin, resulting in destruction of the podocyte cytoskeleton. Saxagliptin may have pleiotropic effects to prevent podocyte injury.

scholarly journals FP128PODOCYTE-ASSOCIATED MESSENGER RNA PROFILES IN LUPUS NEPHRITIS: DOES SEVERITY OF THE HISTOLOGICAL LESIONS HAVE AN EFFECT ON THE INTENSITY OF PODOCYTE INJURY?

2015 ◽  
Vol 30 (suppl_3) ◽  
pp. iii109-iii110
Author(s):  
Francisco V Veronese ◽  
Mariane dos Santos ◽  
Rafael N Bringhenti ◽  
Patrícia G Rodrigues ◽  
Jonathan F do Nascimento ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Messenger Rna ◽  
Podocyte Injury

scholarly journals Astragalus membranaceus and Panax notoginseng, the Novel Renoprotective Compound, Synergistically Protect against Podocyte Injury in Streptozotocin-Induced Diabetic Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Ruonan Zhai ◽  
Guihua Jian ◽  
Teng Chen ◽  
Ling Xie ◽  
Rui Xue ◽  
...  
Keyword(s):  
Panax Notoginseng ◽  
Diabetic Rats ◽  
Astragalus Membranaceus ◽  
Protective Effects ◽  
The Novel ◽  
Podocyte Injury ◽  
Renal Histopathology ◽  
Foot Process ◽  
Immunofluorescence Labeling ◽  
Renal Expression

This study was aimed at investigating the synergistical protective effects of Astragalus membranaceus (AG) and Panax notoginseng (NG) on podocyte injury in diabetic rats. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin at 55 mg/kg. Diabetic rats were then orally administrated with losartan, AG, NG, and AG plus NG (2 : 1) for 12 weeks. Albuminuria, biochemical markers, renal histopathology, and podocyte number per glomerulus were measured. Podocyte apoptosis was determined by triple immunofluorescence labeling including TUNEL assay, WT1, and DAPI. Renal expression of nephrin, α-dystroglycan, Bax, Bcl-xl, and Nox4 was evaluated by immunohistochemistry, western blot, and RT-PCR. AG plus NG ameliorated albuminuria, renal histopathology, and podocyte foot process effacement to a greater degree than did AG or NG alone. The number of podocytes per glomerulus, as well as renal expression of nephrin, α-dystroglycan, and Bcl-xl, was decreased, while podocyte apoptosis, as well as renal expression of Bax and Nox4, was increased in diabetic rats. All of these abnormalities were partially restored by AG plus NG to a greater degree than did AG or NG alone. In conclusion, AG and NG synergistically ameliorated diabetic podocyte injury partly through upregulation of nephrin, α-dystroglycan, and Bcl-xl, as well as downregulation of Bax and Nox4. These findings might provide a novel treatment combination for DN.

scholarly journals Protective effects of DPP-4 inhibitor on podocyte injury in glomerular diseases

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ayano Kubo ◽  
Teruo Hidaka ◽  
Maiko Nakayama ◽  
Yu Sasaki ◽  
Miyuki Takagi ◽  
...  
Keyword(s):  
Proximal Tubules ◽  
Pleiotropic Effects ◽  
Protective Effects ◽  
Crescent Formation ◽  
Glomerular Diseases ◽  
Podocyte Injury ◽  
Dipeptidyl Peptidase 4 ◽  
Anti Oxidant ◽  
Glucagon Like Peptide 1 ◽  
Antigen Antibody

Abstract Background Dipeptidyl peptidase-4 (DPP-4) is a serine protease that inhibits the degradation of glucagon-like peptide 1. DPP-4 inhibitors are used worldwide to treat type 2 diabetes mellitus and were recently shown to have pleiotropic effects such as anti-oxidant, anti-inflammatory, and anti-fibrotic actions. DPP-4 inhibitors improve albuminuria and renal injury including glomerular damage independent of its hypoglycemic effect. Although DPP-4 is mainly expressed in the kidney, the physiological function of DPP-4 remains unclear. Methods The localization of renal DPP-4 activity was determined in human renal biopsy specimens with glycyl-1-prolyl-4-methoxy-2-naphthylamide and the effects of a DPP-4 inhibitor were examined in human cultured podocyte. Results DPP-4 activity under normal conditions was observed in some Bowman’s capsular epithelial cells and proximal tubules, but not in the glomerulus. DPP-4 activity was observed in crescent formation in anti-neutrophil myeloperoxidase cytoplasmic antigen antibody nephritis, nodular lesions in diabetic nephropathy, and some podocytes in focal segmental glomerulosclerosis. Notably, the DPP-4 inhibitor saxagliptin suppressed DPP-4 activity in podocytes and the proximal tubules. To assess the effect of DPP-4 inhibitor on podocytes, human cultured podocytes were injured by Adriamycin, which increased DPP-4 activity; this activity was dose-dependently suppressed by saxagliptin. Treatment with saxagliptin maintained the structure of synaptopodin and RhoA. Saxagliptin also improved the detachment of podocytes. Conclusions DPP-4 activity induces degradation of synaptopodin and reduction of RhoA, resulting in destruction of the podocyte cytoskeleton. Saxagliptin may have pleiotropic effects to prevent podocyte injury.

Protective effects of eplerenone on podocyte injury in adriamycin nephropathy rats

2011 ◽  
Vol 31 (3) ◽  
pp. 329-334 ◽  
Author(s):  
Zhan Fang ◽  
Chun Zhang ◽  
Fangfang He ◽  
Shan Chen ◽  
Xifeng Sun ◽  
...  
Keyword(s):  
Protective Effects ◽  
Podocyte Injury ◽  
Adriamycin Nephropathy

scholarly journals Podocyte Injury in Lupus Nephritis

2019 ◽  
Vol 8 (9) ◽  
pp. 1340 ◽  
Author(s):  
Hamza Sakhi ◽  
Anissa Moktefi ◽  
Khedidja Bouachi ◽  
Vincent Audard ◽  
Carole Hénique ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Glomerular Injury ◽  
Crescent Formation ◽  
Podocyte Injury ◽  
Inflammatory Processes ◽  
Lupus Podocytopathy ◽  
Parietal Epithelial Cells ◽  
Lupus Glomerulonephritis

Systemic lupus erythematosus (SLE) is characterized by a broad spectrum of renal lesions. In lupus glomerulonephritis, histological classifications are based on immune-complex (IC) deposits and hypercellularity lesions (mesangial and/or endocapillary) in the glomeruli. However, there is compelling evidence to suggest that glomerular epithelial cells, and podocytes in particular, are also involved in glomerular injury in patients with SLE. Podocytes now appear to be not only subject to collateral damage due to glomerular capillary lesions secondary to IC and inflammatory processes, but they are also a potential direct target in lupus nephritis. Improvements in our understanding of podocyte injury could improve the classification of lupus glomerulonephritis. Indeed, podocyte injury may be prominent in two major presentations: lupus podocytopathy and glomerular crescent formation, in which glomerular parietal epithelial cells play also a key role. We review here the contribution of podocyte impairment to different presentations of lupus nephritis, focusing on the podocyte signaling pathways involved in these lesions.

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 Protective Effects of Thalidomide on High-Glucose-Induced Podocyte Injury through In Vitro Modulation of Macrophage M1/M2 Differentiation

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Hui Liao ◽  
Yuanping Li ◽  
Xilan Zhang ◽  
Xiaoyun Zhao ◽  
Dan Zheng ◽  
...  
Keyword(s):  
High Glucose ◽  
Macrophage Polarization ◽  
Mannose Receptor ◽  
Raw 264.7 Cells ◽  
Protective Effects ◽  
Activated Macrophages ◽  
Podocyte Injury ◽  
Protein Expressions ◽  
Activated Macrophage

Objective. It has been shown that podocyte injury represents an important pathological basis that contributes to proteinuria and eventually leads to kidney failure. High glucose (HG) activates macrophage polarization, further exacerbating HG-induced podocyte injury. Our previous study on diabetic nephropathy rats indicated that thalidomide (Tha) has renoprotective properties. The present study explored the effects of Tha on mRNA and protein expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor- (TNF-) α, mannose receptor (CD206), and arginase- (Arg-) 1 in HG-activated macrophages. iNOS and TNF-α are established as markers of classically activated macrophage (M1). CD206 and Arg-1 are regarded as markers of alternatively activated macrophages (M2). During the experiment, the supernatants of (HG)-treated and (Tha)-treated macrophages, designated as (HG) MS and (Tha) MS, were simultaneously collected and processed. TNF-α and interleukin- (IL-) 1β levels as well as protein expressions of nephrin and podocin in HG, (HG) MS, and (Tha) MS-cultured podocytes were evaluated. The results showed that compared to the 11.1 mM normal glucose (NG), the 33.3 mM HG-cultured RAW 264.7 cells exhibited upregulated iNOS and TNF-α mRNAs and protein expressions, and downregulated CD206 and Arg-1 expressions significantly (p<0.05). Tha 200 μg/ml suppressed iNOS and TNF-α, and promoted CD206 and Arg-1 expressions significantly compared to the HG group (p<0.05). Furthermore, (HG) MS-treated podocytes showed an increase in TNF-α and IL-1β levels and a downregulation in nephrin and podocin expression significantly compared to NG-treated and HG-treated podocytes (p<0.05). The (Tha 200 μg/ml) MS group exhibited a decrease in TNF-α and IL-1β level, and an upregulation in nephrin and podocin expressions significantly compared to the (HG) MS group (p<0.05). Our research confirmed that HG-activated macrophage differentiation aggravates HG-induced podocyte injury in vitro and the protective effects of Tha might be related to its actions on TNF-α and IL-1β levels via its modulation on M1/M2 differentiation.

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