P62 The effects of type I IGF receptor inhibition with small-molecule diarylureas in a mouse model of type I diabetic kidney disease

2010 ◽  
Vol 20 ◽  
pp. S61
Author(s):  
A. Troib ◽  
D. Wiezel
Keyword(s):  
Kidney Disease ◽  
Mouse Model ◽  
Small Molecule ◽  
Diabetic Kidney Disease ◽  
Type I ◽  
Diabetic Kidney ◽  
Receptor Inhibition ◽  
Type I Igf Receptor ◽  
Igf Receptor

scholarly journals The effects of type 1 IGF receptor inhibition in a mouse model of diabetic kidney disease

2011 ◽  
Vol 21 (5) ◽  
pp. 285-291 ◽  
Author(s):  
Ariel Troib ◽  
Daniel Landau ◽  
Jack F. Youngren ◽  
Leonid Kachko ◽  
Ralph Rabkin ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Mouse Model ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Receptor Inhibition ◽  
Igf Receptor

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 Key profibrotic and pro-inflammatory pathways in the pathogenesis of diabetic kidney disease

2021 ◽  
Vol 1 (1) ◽  
pp. 15-26
Author(s):  
Devang M. Patel ◽  
Yuxin Yang ◽  
Kexin Shi ◽  
Tieqiao Wu ◽  
Mark E. Cooper ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Renal Fibrosis ◽  
Diabetic Kidney Disease ◽  
Transforming Growth Factor ◽  
Large Body ◽  
Noncommunicable Disease ◽  
Sirtuin 1 ◽  
Type I ◽  
Diabetic Kidney ◽  
Inflammatory Pathways

Abstract Diabetes is a noncommunicable disease and arguably represents the greatest pandemic in human history. Diabetic kidney disease (DKD) is seen in both type 1 and type 2 diabetes and can be detected in up to 30–50% of diabetic subjects. DKD is a progressive chronic kidney disease (CKD) and is a leading cause of mortality and morbidity in patients with diabetes. Renal fibrosis and inflammation are the major pathological features of DKD. There are a large number of independent and overlapping profibrotic and pro-inflammatory pathways involved in the pathogenesis and progression of DKD. Among these pathways, the transforming growth factor-β (TGF-β) pathway plays a key pathological role by promoting fibrosis. Sirtuin-1 (SIRT1) is a protein deacetylase that has been shown to be renoprotective with an anti-inflammatory effect. It is postulated that a reduction in renal SIRT1 levels could play a key role in the pathogenesis of DKD and that restoration of SIRT1 will attenuate DKD. Cell division autoantigen 1 (CDA1) synergistically enhances the profibrotic effect of TGF-β in DKD by regulating the expression of the TGF-β type I receptor (TβRI). CDA1 has also been found to be an inhibitor of SIRT1 in the DNA damage response. Indeed, targeting CDA1 in experimental DKD not only attenuates diabetes-associated renal fibrosis but also attenuates the expression of key pro-inflammatory genes such as tumor necrosis factor-α (TNF-α) and Monocyte Che moattractant Protein-1 (MCP-1). In conclusion, there is a large body of experimental data to support the view that targeting CDA1 is a superior approach to directly targeting TGF-β in DKD since it is not only safe but also efficacious in retarding both fibrosis and inflammation.

scholarly journals C-reactive protein promotes diabetic kidney disease in a mouse model of type 1 diabetes

Diabetologia ◽  
2011 ◽  
Vol 54 (10) ◽  
pp. 2713-2723 ◽  
Author(s):  
F. Liu ◽  
H. Y. Chen ◽  
X. R. Huang ◽  
A. C. K. Chung ◽  
L. Zhou ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Kidney Disease ◽  
Mouse Model ◽  
Diabetic Kidney Disease ◽  
C Reactive Protein ◽  
Diabetic Kidney ◽  
Reactive Protein

scholarly journals Mesangial matrix expansion in a novel mouse model of diabetic kidney disease associated with the metabolic syndrome

2020 ◽  
Vol 10 (2) ◽  
pp. e17-e17
Author(s):  
Elisabet Van Loon ◽  
Joseph Pierre Aboumsallem ◽  
Evelyne Lerut ◽  
Marija Bogojevic ◽  
Aleksandar Denic ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Kidney Disease ◽  
Mouse Model ◽  
Diabetic Kidney Disease ◽  
Mesangial Matrix ◽  
Diabetic Kidney ◽  
The Metabolic Syndrome ◽  
Matrix Expansion

Effect of the Novel Compound SMTP‐27 in a Mouse Model of Diabetic Kidney Disease

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Keita Shibata ◽  
Erika Yasuda ◽  
Tomoka Nishinaga ◽  
Sarara Karasawa ◽  
Tomoaki Yamaguchi ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Mouse Model ◽  
Diabetic Kidney Disease ◽  
The Novel ◽  
Diabetic Kidney

Renal type I inositol 1,4,5-trisphosphate receptor is reduced in streptozotocin-induced diabetic rats and mice

1999 ◽  
Vol 276 (1) ◽  
pp. F54-F61 ◽  
Author(s):  
Kumar Sharma ◽  
Lewei Wang ◽  
Yanqing Zhu ◽  
Aurora DeGuzman ◽  
Gao-Yuan Cao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Diabetic Rats ◽  
Type I ◽  
Renal Hypertrophy ◽  
Diabetic Kidney ◽  
Inositol 1,4,5 Trisphosphate ◽  
Rats And Mice ◽  
Tgf Β1

The mechanisms underlying glomerular hypertrophy and hyperfiltration in diabetes remain unclear. We have previously demonstrated that the cytokine transforming growth factor-β1 (TGF-β1) is increased in early diabetic kidney disease and TGF-β1 inhibits the expression of the inositol 1,4,5-trisphosphate (IP3)-gated calcium channel, the type I IP3 receptor (IP3R), in mesangial cells. To test the hypothesis that reduced type I IP3R may be important in diabetic kidney disease, we evaluated type I IP3R expression in the kidney of streptozotocin-induced diabetic rats and mice. Two-week-old diabetic rats have decreased renal type I IP3R protein and mRNA levels. Immunostaining of normal rat kidney demonstrated presence of type I IP3R in glomerular and vascular smooth muscle cells, whereas diabetic rats had reduced staining in both compartments. Reduction of type I IP3R also occurred in parallel with renal hypertrophy, increased creatinine clearance, and increased renal TGF-β1 expression in the diabetic rats. Two-week-old diabetic mice also had reduced renal type I IP3R protein and mRNA expression in association with renal hypertrophy and increased TGF-β1 mRNA expression. These findings demonstrate that there is reduced type I IP3R in glomerular and vascular smooth muscle cells in the diabetic kidney, which may contribute to the altered renal vasoregulation and renal hypertrophy of diabetes.

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