Podocyte Loss and Progression of Diabetic Nephropathy

2001 ◽  
pp. 69-73 ◽  
Author(s):  
I. Shirato ◽  
T. Hishiki ◽  
Y. Tomino
Keyword(s):  
Diabetic Nephropathy ◽  
Podocyte Loss

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 ACE-inhibitors but not endothelin receptor blockers prevent podocyte loss in early diabetic nephropathy

Diabetologia ◽  
2003 ◽  
Vol 46 (6) ◽  
pp. 856-868 ◽  
Author(s):  
A. Koch ◽  
A. Kuhlmann ◽  
K. M�nter ◽  
E. Ritz ◽  
K. Amann ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Ace Inhibitors ◽  
Endothelin Receptor ◽  
Podocyte Loss ◽  
Receptor Blockers ◽  
Early Diabetic Nephropathy

scholarly journals Reduction of VEGF-A and CTGF expression in diabetic nephropathy is associated with podocyte loss

2007 ◽  
Vol 71 (7) ◽  
pp. 637-645 ◽  
Author(s):  
H.-J. Baelde ◽  
M. Eikmans ◽  
D.W.P. Lappin ◽  
P.P. Doran ◽  
D. Hohenadel ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Podocyte Loss

MO628IMPACT OF INDUCTION OF AUTOPHAGY BY RAPAMYCIN AND METFORMIN ON NATURAL HISTORY OF DIABETIC NEPHROPATHY IN RATS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Samar Ahmed ◽  
Emad Samaan ◽  
Dina Abdallah Ibrahim ◽  
Nagy Sayed-Ahmed ◽  
Hussein Sheashaa
Keyword(s):  
Diabetic Nephropathy ◽  
Therapeutic Option ◽  
Total Duration ◽  
Kidney Tissue ◽  
Diabetic Rats ◽  
Normal Serum ◽  
Control Group ◽  
Podocyte Loss ◽  
Healthy Control ◽  
History Of

Abstract Background and Aims Impaired autophagy in the kidney resulted in podocyte loss and massive proteinuria in diabetic nephropathy. Improvement of autophagy by activation of mTORC1 and reduction of AMPK and Sirt1 may be a novel therapeutic option for the suppression of diabetic nephropathy. Method This experimental work was carried out on 48 adult male Sprague dawely rats. The total duration of the study was 10 weeks. All investigation and intervention were carried out at 3 time points, 3 weeks, 6 weeks, 10 weeks. The rats were randomly divided into healthy control group (n = 12) and 3 induced diabetic groups (n = 12 each), the three groups were the non-treated, treated with rapamycin and treated with rapamycin and metformin. To study autophagy, we use electron microscopy and immunohistochemical staining of kidney tissue with LC3 antibody Results Diabetic rats treated with rapamycin alone or rapamycin and metformin showed lower level of proteinuria and almost normal serum creatinine through all intervals of the study. Also, their Kidney tissue showed increased autophagosomes and high expression of LC3 compared to diabetic rats. There are no significant differences between both treated groups in terms of induction of autophagy during the experiment period. Conclusion we concluded that using a small dose of rapamycin for short duration in early diabetic rats is beneficial in halting the course of diabetic nephropathy, adding metformin to rapamycin aiming to potentiate its effect on autophagy seems to be less beneficial.

Erythropoietin ameliorates podocyte injury in advanced diabetic nephropathy in the db/db mouse

2013 ◽  
Vol 305 (6) ◽  
pp. F911-F918 ◽  
Author(s):  
Ivonne Loeffler ◽  
Christiane Rüster ◽  
Sybille Franke ◽  
Marita Liebisch ◽  
Gunter Wolf
Keyword(s):  
Body Weight ◽  
Diabetic Nephropathy ◽  
Treatment Group ◽  
Group Versus ◽  
Erythropoietin Receptor ◽  
Protective Effects ◽  
Creatinine Ratio ◽  
Renal Hypertrophy ◽  
Podocyte Loss

Podocyte damage and accumulation of advanced glycation end products (AGEs) are characteristics of diabetic nephropathy (DN). The pathophysiology of AGE-challenged podocytes, such as hypertrophy, apoptosis, and reduced cell migration, is closely related to the induction of the cell cycle inhibitor p27Kip1 and to the inhibition of neuropilin 1 (NRP1). We have previously demonstrated that treatment with erythropoietin is associated with protective effects for podocytes in vitro. db/ db mice with overt DN aged 15–16 wk were treated with either placebo, epoetin-β, or continuous erythropoietin receptor activator (CERA) for 2 wk. db/ db mice compared with nondiabetic db/ m control mice revealed the expected increases in body weight, blood glucose, albumin-to-creatinine ratio, and AGE accumulation. Whereas there were no differences in body weight, hyperglycemia and AGEs were observed among diabetic mice that received epoetin-β compared with CERA and placebo treatment, indicating that epoetin-β/CERA treatment does not interfere with the development of diabetes in this model. However, the albumin-to-creatinine ratio was significantly lower in db/ db mice treated with epoetin-β or CERA. Furthermore, kidney weights in db/ db mice were increased compared with db/ m control mice, indicating renal hypertrophy, whereas the increase in renal weight in epoetin-β- or CERA-treated db/ db mice was significantly lower than in placebo-treated control mice. Induction of p27Kip1 and suppression of NRP1 were significantly reduced in the epoetin-β treatment group versus the CERA treatment group. Furthermore, erythropoietin treatment diminished the diabetes-induced podocyte loss. Together, independently from hematopoetic effects, epoetin-β or CERA treatment was associated with protective changes in DN, especially that NRP1 and p27Kip1 expressions as well as numbers of podocytes returned to normal levels. Our data show, for the first time, that medication of overt DN with erythropoietin for a short time can ameliorate albuminuria and podocyte loss.

scholarly journals Podocyte loss and albuminuria of KK-Ay mouse: A spontaneous animal model for human type 2 diabetic nephropathy

2012 ◽  
Vol 02 (03) ◽  
pp. 346-352 ◽  
Author(s):  
Yuji Ishikawa ◽  
Takamichi Ito ◽  
Mitsuo Tanimoto ◽  
Shinji Hagiwara ◽  
Masako Furukawa ◽  
...  
Keyword(s):  
Animal Model ◽  
Diabetic Nephropathy ◽  
Human Type ◽  
Podocyte Loss ◽  
Spontaneous Animal Model ◽  
Type 2 Diabetic

Beneficial effect on podocyte number in experimental diabetic nephropathy resulting from combined atrasentan and RAAS inhibition therapy

2020 ◽  
Vol 318 (5) ◽  
pp. F1295-F1305 ◽  
Author(s):  
Kelly L. Hudkins ◽  
Tomasz A. Wietecha ◽  
Floor Steegh ◽  
Charles E. Alpers
Keyword(s):  
Diabetic Nephropathy ◽  
Underlying Mechanism ◽  
Therapeutic Benefit ◽  
Functional Improvement ◽  
Collagen Type Iv ◽  
Mesangial Matrix ◽  
Similar Treatment ◽  
Type Iv ◽  
Podocyte Loss ◽  
Patients With Diabetes

Podocyte loss and proteinuria are both key features of human diabetic nephropathy (DN). The leptin-deficient BTBR mouse strain with the ob/ob mutation develops progressive weight gain, type 2 diabetes, and diabetic nephropathy that has many features of advanced human DN, including increased mesangial matrix, mesangiolysis, podocyte loss, and proteinuria. Selective antagonism of the endothelin-1 type A receptor (ETAR) by atrasentan treatment in combination with renin-angiotensin-aldosterone system inhibition with losartan has been shown to have the therapeutic benefit of lowering proteinuria in patients with DN, but the underlying mechanism for this benefit is not well understood. Using a similar therapeutic approach in diabetic BTBR ob/ob mice, this treatment regimen significantly increased glomerular podocyte number compared with diabetic BTBR ob/ob controls and suggested that parietal epithelial cells were a source for podocyte restoration. Atrasentan treatment alone also increased podocyte number but to a lesser degree. Mice treated with atrasentan demonstrated a reduction in proteinuria, matching the functional improvement reported in humans. This is a first demonstration that treatment with the highly selective ETAR antagonist atrasentan can lead to restoration of the diminished podocyte number characteristic of DN in humans and thereby underlies the reduction in proteinuria in patients with diabetes undergoing similar treatment. The benefit of ETAR antagonism in DN extended to a decrease in mesangial matrix as measured by a reduction in accumulations of collagen type IV in both the atrasentan and atrasentan + losartan-treated groups compared with untreated controls.

scholarly journals YAP Translocation Precedes Cytoskeletal Rearrangement in Podocyte Stress Response: A Podometric Investigation of Diabetic Nephropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Kathryn E. Haley ◽  
Mustafa Elshani ◽  
In Hwa Um ◽  
Cameron Bell ◽  
Peter D. Caie ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Underlying Mechanism ◽  
Glomerular Disease ◽  
Automated Image Analysis ◽  
Podocyte Injury ◽  
Cytoskeletal Rearrangement ◽  
Viable Cells ◽  
Podocyte Loss ◽  
Cytoplasmic Translocation ◽  
Grade Iii

Podocyte loss plays a pivotal role in the pathogenesis of glomerular disease. However, the mechanisms underlying podocyte damage and loss remain poorly understood. Although detachment of viable cells has been documented in experimental Diabetic Nephropathy, correlations between reduced podocyte density and disease severity have not yet been established. YAP, a mechanosensing protein, has recently been shown to correlate with glomerular disease progression, however, the underlying mechanism has yet to be fully elucidated. In this study, we sought to document podocyte density in Diabetic Nephropathy using an amended podometric methodology, and to investigate the interplay between YAP and cytoskeletal integrity during podocyte injury. Podocyte density was quantified using TLE4 and GLEPP1 multiplexed immunofluorescence. Fourteen Diabetic Nephropathy cases were analyzed for both podocyte density and cytoplasmic translocation of YAP via automated image analysis. We demonstrate a significant decrease in podocyte density in Grade III/IV cases (124.5 per 106 μm3) relative to Grade I/II cases (226 per 106 μm3) (Student’s t-test, p < 0.001), and further show that YAP translocation precedes cytoskeletal rearrangement following injury. Based on these findings we hypothesize that a significant decrease in podocyte density in late grade Diabetic Nephropathy may be explained by early cytoplasmic translocation of YAP.

scholarly journals Combined inhibition of CCR2 and ACE provides added protection against progression of diabetic nephropathy in Nos3-deficient mice

2019 ◽  
Vol 317 (6) ◽  
pp. F1439-F1449 ◽  
Author(s):  
Gregory H. Tesch ◽  
Nick Pullen ◽  
Michael I. Jesson ◽  
Franklin J. Schlerman ◽  
David J. Nikolic-Paterson
Keyword(s):  
Renal Function ◽  
Diabetic Nephropathy ◽  
Early Intervention ◽  
Renal Dysfunction ◽  
Diabetic Glomerulosclerosis ◽  
Renal Function Impairment ◽  
Late Intervention ◽  
Podocyte Loss ◽  
Function Impairment ◽  
Deficient Mice

Macrophage-mediated renal injury promotes the development of diabetic nephropathy. Blockade of chemokine (C-C motif) receptor 2 (CCR2) inhibits kidney macrophage accumulation and early glomerular damage in diabetic animals. This study tested early and late interventions with a CCR2 antagonist (CCR2A) in a model of progressive diabetic glomerulosclerosis and determined whether CCR2A provides added benefit over conventional treatment with an angiotensin-converting enzyme inhibitor (ACEi). Diabetes was induced in hypertensive endothelial nitric oxide synthase ( Nos3)-deficient mice by administration of five low-dose streptozotocin (STZ) injections daily. Groups of diabetic Nos3−/− mice received a CCR2A (30 mg·kg−1·day−1 PF-04634817 in chow) as an early intervention ( weeks 2–15 after STZ). The late intervention ( weeks 8–15 after STZ) involved PF-04634817 alone, ACEi (captopril in water 10 mg·kg−1·day−1) alone, or combined ACEi + CCR2A. Control diabetic and nondiabetic Nos3−/− mice received normal chow and water. Early intervention with a CCR2A inhibited kidney inflammation and glomerulosclerosis, albuminuria, podocyte loss, and renal function impairment but not hypertension in diabetic Nos3−/− mice. Late intervention with a CCR2A also inhibited kidney inflammation, glomerulosclerosis, and renal dysfunction but did not affect albuminuria. ACEi alone suppressed hypertension and albuminuria and partially reduced podocyte loss and glomerulosclerosis but did not affect renal dysfunction. Compared with ACEi alone, the combined late intervention with ACEi + CCR2A provided better protection against kidney damage (inflammation, glomerulosclerosis, and renal function impairment) but not albuminuria. In conclusion, this study demonstrates that combining CCR2A and ACEi provides broader and superior renal protection than ACEi alone in a model of established diabetic glomerulosclerosis with hypertension.

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