scholarly journals Research Progress on the Pathological Mechanisms of Podocytes in Diabetic Nephropathy

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Lili Zhang ◽  
Zhige Wen ◽  
Lin Han ◽  
Yujiao Zheng ◽  
Yu Wei ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Morphological Changes ◽  
Research Progress ◽  
Podocyte Injury ◽  
Functional Changes ◽  
Pathological Mechanism ◽  
Podocyte Detachment ◽  
Stage Renal Disease ◽  
End Stage ◽  
Multiple Signaling

Diabetic nephropathy (DN) is not only an important microvascular complication of diabetes but also the main cause of end-stage renal disease. Studies have shown that the occurrence and development of DN are closely related to morphological and functional changes in podocytes. A series of morphological changes after podocyte injury in DN mainly include podocyte hypertrophy, podocyte epithelial-mesenchymal transdifferentiation, podocyte detachment, and podocyte apoptosis; functional changes mainly involve podocyte autophagy. More and more studies have shown that multiple signaling pathways play important roles in the progression of podocyte injury in DN. Here, we review research progress on the pathological mechanism of morphological and functional changes in podocytes associated with DN, to provide a new target for delaying the occurrence and development of this disorder.

scholarly journals Tiaolipiwei Acupuncture Reduces Albuminuria by Alleviating Podocyte Lesions in a Rat Model of Diabetic Nephropathy

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Zhilong Zhang ◽  
Xinju Li ◽  
Liang Liu ◽  
Jiya Sun ◽  
Xu Wang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Rat Model ◽  
Morphological Changes ◽  
Renal Tissue ◽  
Transmission Electron ◽  
End Of Treatment ◽  
Stage Renal Disease ◽  
End Stage ◽  
Protein Serum

Background. Diabetic nephropathy is a common and serious complication of diabetes and a major cause of end-stage renal disease. Tiaolipiwei acupuncture is a safe treatment approach that may be effective for lowering albuminuria in diabetic nephropathy. Yet, the exact mechanisms of this therapeutic effect are unclear. Methods. A rodent model of type 2 diabetic nephropathy (T2DN) was induced by a high-fat diet combined with low-dose streptozotocin. T2DN rats were treated with Tiaolipiwei acupuncture (ACU) for 4, 8, or 12 weeks. At the end of treatment, urinary and blood samples were collected for analysis. Transmission electron microscopy was used to observe morphological changes, and protein expression levels of nephrin, CD2AP, podocalyxin, and desmin were quantified in renal tissue. Results. Compared to the T2DN groups, the T2DN + ACU groups showed significant improvements in 24-hour urinary protein, serum urea, cholesterol, and triglycerides at all time points. ACU treatment also improved the density of slit diaphragms. Simultaneously, ACU promoted the renal expression of nephrin, CD2AP, and podocalyxin and decreased the expression of desmin. Conclusion. Our study suggests that Tiaolipiwei acupuncture ameliorates podocyte lesions to reduce albuminuria and prevent the progression of T2DN in a rat model.

scholarly journals Carvedilol Ameliorates Early Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Mohamed A. Morsy ◽  
Salwa A. Ibrahim ◽  
Entesar F. Amin ◽  
Maha Y. Kamel ◽  
Soha A. Abdelwahab ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Protective Effect ◽  
Histopathological Examination ◽  
Electron Microscopic Examination ◽  
Diabetic Rats ◽  
Electron Microscopic ◽  
Podocyte Injury ◽  
Stage Renal Disease ◽  
End Stage ◽  
Early Diabetic Nephropathy

Diabetic nephropathy results in end-stage renal disease. On the other hand, carvedilol has been reported to have various pharmacological properties. The aim of this study therefore is to evaluate the possible protective effect of carvedilol on streptozotocin-induced early diabetic nephropathy and various mechanisms underlie this effect in rats. Single i.p. injection of streptozotocin (65 mg/kg) was administered to induce early diabetic nephropathy in Wistar rats. Oral administration of carvedilol at a dose level of 1 and 10 mg/kg daily for 4 weeks resulted in nephroprotective effect as evident by significant decrease in serum creatinine level, urinary albumin/creatinine ratio, and kidney index as well as renal levels of malondialdehyde, nitric oxide, tumor necrosis factor-α, and cyclooxygenase-2 with a concurrent increase in creatinine clearance and renal reduced glutathione level compared to diabetic untreated rats. The protective effect of carvedilol was confirmed by renal histopathological examination. The electron microscopic examination indicated that carvedilol could effectively ameliorate glomerular basement membrane thickening and podocyte injury. In conclusion, carvedilol protects rats against streptozotocin-induced early diabetic nephropathy possibly, in part, through its antioxidant as well as anti-inflammatory activities, and ameliorating podocyte injury.

scholarly journals Silencing of miR-150-5p Ameliorates Diabetic Nephropathy by Targeting SIRT1/p53/AMPK Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenmin Dong ◽  
Huiqian Zhang ◽  
Cheng Zhao ◽  
Yun Luo ◽  
Ying Chen
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Tissue ◽  
Protective Role ◽  
Sirtuin 1 ◽  
Podocyte Injury ◽  
Stage Renal Disease ◽  
End Stage ◽  
Amp Activated Protein Kinase

Diabetic nephropathy (DN) is a common complication of diabetes and an important cause of end-stage renal disease. Increasing evidence suggests that microRNAs (miRNAs) regulate the development of DN. In a preliminary study, high levels of miR-150-5p were detected in the serum and urine of patients with DN. Consequently, we investigated the effect and mechanism of action of miR-150-5p in DN in vitro and in vivo. Our results showed that inhibition of miR-150-5p reversed high glucose-induced podocyte injury and Streptozocin (STZ)-induced diabetic nephropathy in mice. Further analysis revealed that miR-150-5p targeted the 3′ untranslated region (UTR) of sirtuin 1 (SIRT1), consequently decreasing SIRT1 levels in podocytes. Importantly, we found that the silencing of miR-150-5p promoted the interaction between SIRT1 and p53, causing the suppression of p53 acetylation in podocytes and kidney tissue. This resulted in the stimulation of AMP-activated protein kinase (AMPK)-dependent autophagy. In conclusion, our study demonstrated that the silencing of miR-150-5p played a reno-protective role in DN mice through targeting SIRT1.

L-carnosine and its Derivatives as New Therapeutic Agents for the Prevention and Treatment of Vascular Complications of Diabetes

2020 ◽  
Vol 27 (11) ◽  
pp. 1744-1763 ◽  
Author(s):  
Stefano Menini ◽  
Carla Iacobini ◽  
Claudia Blasetti Fantauzzi ◽  
Giuseppe Pugliese
Keyword(s):  
Diabetic Nephropathy ◽  
Life Quality ◽  
Vascular Complications ◽  
Carbonyl Stress ◽  
Complications Of Diabetes ◽  
Diabetic Vascular Complications ◽  
Reactive Carbonyl Species ◽  
Stage Renal Disease ◽  
Stress Dependent ◽  
End Stage

Vascular complications are among the most serious manifestations of diabetes. Atherosclerosis is the main cause of reduced life quality and expectancy in diabetics, whereas diabetic nephropathy and retinopathy are the most common causes of end-stage renal disease and blindness. An effective therapeutic approach to prevent vascular complications should counteract the mechanisms of injury. Among them, the toxic effects of Advanced Glycation (AGEs) and Lipoxidation (ALEs) end-products are well-recognized contributors to these sequelae. L-carnosine (β-alanyl-Lhistidine) acts as a quencher of the AGE/ALE precursors Reactive Carbonyl Species (RCS), which are highly reactive aldehydes derived from oxidative and non-oxidative modifications of sugars and lipids. Consistently, L-carnosine was found to be effective in several disease models in which glyco/lipoxidation plays a central pathogenic role. Unfortunately, in humans, L-carnosine is rapidly inactivated by serum carnosinase. Therefore, the search for carnosinase-resistant derivatives of Lcarnosine represents a suitable strategy against carbonyl stress-dependent disorders, particularly diabetic vascular complications. In this review, we present and discuss available data on the efficacy of L-carnosine and its derivatives in preventing vascular complications in rodent models of diabetes and metabolic syndrome. We also discuss genetic findings providing evidence for the involvement of the carnosinase/L-carnosine system in the risk of developing diabetic nephropathy and for preferring the use of carnosinase-resistant compounds in human disease. The availability of therapeutic strategies capable to prevent both long-term glucose toxicity, resulting from insufficient glucoselowering therapy, and lipotoxicity may help reduce the clinical and economic burden of vascular complications of diabetes and related metabolic disorders.

scholarly journals Herba Artemisiae Capillaris Extract Prevents the Development of Streptozotocin-Induced Diabetic Nephropathy of Rat

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Jianan Geng ◽  
Xiaoyan Yu ◽  
Chunyu Liu ◽  
Chengbo Sun ◽  
Menghuan Guo ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Tissue Transglutaminase ◽  
Blood Lipid ◽  
High Dose ◽  
Oxygen Species ◽  
Promising Candidate ◽  
Ecm Degradation ◽  
Stage Renal Disease ◽  
End Stage ◽  
Excessive Accumulation

Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world; until now there is no specific drug available. In this work, we use herba artemisiae capillaris extract (HACE) to alleviate renal fibrosis characterized by the excessive accumulation of extracellular matrix (ECM) in rats, aiming to investigate the protective effect of the HACE on DN. We found that the intragastric treatment of high-dose HACE could reverse the effect of streptozotocin not only to decrease the level of blood glucose and blood lipid in different degree but also further to improve renal functions. It is worth mentioning that the effect of HACE treatment was comparable to the positive drug benazepril. Moreover, we found that HACE treatment could on one hand inhibit oxidative stress in DN rats through regulating enzymatic activity for scavenging reactive oxygen species and on the other hand increase the ECM degradation through regulating the activity of metalloproteinase-2 (MMP-2) and the expression of tissue transglutaminase (tTG), which explained why HACE treatment inhibited ECM accumulation. On the basis of above experimental results, we conclude that HACE prevents DN development in a streptozotocin-induced DN rat model, and HACE is a promising candidate to cure DN in clinic.

scholarly journals Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 457
Author(s):  
Kyeong-Seok Kim ◽  
Jin-Sol Lee ◽  
Jae-Hyeon Park ◽  
Eun-Young Lee ◽  
Jong-Seok Moon ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Early Stage ◽  
Kidney Injury ◽  
Diabetic Patients ◽  
High Morbidity ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Zucker Diabetic Fatty Rats ◽  
Kidney Injury Molecule 1 ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.

Diabetic kidney disease in thedb/dbmouse

2003 ◽  
Vol 284 (6) ◽  
pp. F1138-F1144 ◽  
Author(s):  
Kumar Sharma ◽  
Peter McCue ◽  
Stephen R. Dunn
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Mouse Model ◽  
Renal Disease ◽  
Mouse Models ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Matrix Expansion ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy is increasing in incidence and is now the number one cause of end-stage renal disease in the industrialized world. To gain insight into the genetic susceptibility and pathophysiology of diabetic nephropathy, an appropriate mouse model of diabetic nephropathy would be critical. A large number of mouse models of diabetes have been identified and their kidney disease characterized to various degrees. Perhaps the best characterized and most intensively investigated model is the db/ db mouse. Because this model appears to exhibit the most consistent and robust increase in albuminuria and mesangial matrix expansion, it has been used as a model of progressive diabetic renal disease. In this review, we present the findings from various studies on the renal pathology of the db/ db mouse model of diabetes in the context of human diabetic nephropathy. Furthermore, we discuss shortfalls of assessing functional renal disease in mouse models of diabetic kidney disease.

scholarly journals High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy

2016 ◽  
Vol 113 (8) ◽  
pp. 2218-2222 ◽  
Author(s):  
Catherine K. Hathaway ◽  
Albert S. Chang ◽  
Ruriko Grant ◽  
Hyung-Suk Kim ◽  
Victoria J. Madden ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Transforming Growth Factor ◽  
Association Studies ◽  
Lipid Peroxides ◽  
Transforming Growth Factor Β1 ◽  
Genome Wide Association Studies ◽  
Diabetic Mice ◽  
Stage Renal Disease ◽  
End Stage

Human genome-wide association studies have demonstrated that polymorphisms in the engulfment and cell motility protein 1 gene (ELMO1) are strongly associated with susceptibility to diabetic nephropathy. However, proof of causation is lacking. To test whether modest changes in its expression alter the severity of the renal phenotype in diabetic mice, we have generated mice that are type 1 diabetic because they have the Ins2Akita gene, and also have genetically graded expression of Elmo1 in all tissues ranging in five steps from ∼30% to ∼200% normal. We here show that the Elmo1 hypermorphs have albuminuria, glomerulosclerosis, and changes in the ultrastructure of the glomerular basement membrane that increase in severity in parallel with the expression of Elmo 1. Progressive changes in renal mRNA expression of transforming growth factor β1 (TGFβ1), endothelin-1, and NAD(P)H oxidase 4 also occur in parallel with Elmo1, as do the plasma levels of cystatin C, lipid peroxides, and TGFβ1, and erythrocyte levels of reduced glutathione. In contrast, Akita type 1 diabetic mice with below-normal Elmo1 expression have reduced expression of these various factors and less severe diabetic complications. Remarkably, the reduced Elmo1 expression in the 30% hypomorphs almost abolishes the pathological features of diabetic nephropathy, although it does not affect the hyperglycemia caused by the Akita mutation. Thus, ELMO1 plays an important role in the development of type 1 diabetic nephropathy, and its inhibition could be a promising option for slowing or preventing progression of the condition to end-stage renal disease.

Evidence of α1-adrenoceptor functional changes in omental arteries of patients with end-stage renal disease

2008 ◽  
Vol 28 (1) ◽  
pp. 19-27 ◽  
Author(s):  
M. P. Cruz-Domínguez ◽  
R. Villalobos-Molina ◽  
A. Miliar-García ◽  
D. H. Montes-Cortés ◽  
A. C. Reséndiz-Ramírez ◽  
...  
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Functional Changes ◽  
Stage Renal Disease ◽  
End Stage

Podocalyxin as an early marker predicting diabetic nephropathy and its correlation with stages of diabetic nephropathy in type two diabetic patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Salah El-Din A Shelbaya ◽  
Hanan M Ali ◽  
Rana H Ibrahim ◽  
Nourhan Safwat Sawirs
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Control Group ◽  
Diabetic Patients ◽  
Type 2 Dm ◽  
Stage Renal Disease ◽  
End Stage ◽  
Positive Significant Correlation

Abstract Background Nephropathy, a major complication of diabetes, is the leading cause of end-stage renal disease. Early identification of nephropathy in diabetes patients is crucial because it creates opportunity for preventing the incidence of DN and/or even slows down the process of end-stage renal disease attributed to diabetes. Human podocytes (Pods) have been demonstrated to be functionally and structurally injured in the natural history of diabetic nephropathy. Aim of the Work To evaluate the possible association between the urinary podocalyxin levels and severity and grade of diabetic nephropathy and to use urinary podocalyxin as a non-invasive marker for early stage of diabetic nephropathy in type 2 DM. Patients and Methods We collected 60 known clinically and biochemically type 2 diabetic patients.20 diabetic patients with no evidence of diabetic nephropathy, 20 patients diagnosed as diabetic nephropathy in microalbuminuria stages and 20 patients diagnosed as diabetic nephropathy in macroalbuminuria stages from Ain Shams University hospitals between April and December 2018 and 20 apparently healthy volunteers will included as a control group. Results Urinary PCX was significantly higher in patients group compared to control group. Urinary PCX was significantly higher in microalbuminuric group than in normoalbuminuric group and higher in macroalbuminuric group than in microalbuminuric group. There was a positive significant correlation between FBS, 2HrPP, HBA1C and urinary PCX. There was a positive significant correlation between s.create and urinary PCX. There was a positive significant correlation between ACR and urinary PCX. Conclusion Urinary podocalyxin seems to be beneficial as an early marker for early stages of diabetic nephropathy in type 2 DM patients.

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