scholarly journals Autophagy in diabetic nephropathy

2014 ◽  
Vol 224 (1) ◽  
pp. R15-R30 ◽  
Author(s):  
Yan Ding ◽  
Mary E Choi
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Transforming Growth Factor ◽  
Renin Angiotensin System ◽  
Human Kidney ◽  
Nutrient Sensing ◽  
Signal Pathways ◽  
End Stage

Diabetic nephropathy (DN) is the most common cause of end-stage kidney disease worldwide, and is associated with increased morbidity and mortality in patients with both type 1 and type 2 diabetes. Increasing prevalence of diabetes has made the need for effective treatment of DN critical and thereby identifying new therapeutic targets to improve clinical management. Autophagy is a highly conserved ‘self-eating’ pathway by which cells degrade and recycle macromolecules and organelles. Autophagy serves as an essential mechanism to maintain homeostasis of glomeruli and tubules, and plays important roles in human health and diseases. Impairment of autophagy is implicated in the pathogenesis of DN. Emerging body of evidence suggests that targeting the autophagic pathway to activate and restore autophagy activity may be renoprotective. In this review, we examine current advances in our understanding of the roles of autophagy in diabetic kidney injury, focusing on studies in renal cells in culture, human kidney tissues, and experimental animal models of diabetes. We discuss the major nutrient-sensing signal pathways and diabetes-induced altered intracellular metabolism and cellular events, including accumulation of advanced glycation end-products, increased oxidative stress, endoplasmic reticulum stress, hypoxia, and activation of the renin–angiotensin system, which modulate autophagic activity and contribute to the development of DN. We also highlight recent studies of autophagy and transforming growth factor-β in renal fibrosis, the final common response to injury that ultimately leads to end-stage kidney failure in both type 1 and type 2 diabetes. These findings suggest the possibility that autophagy can be a therapeutic target against DN.

Maternal history of type 2 diabetes is associated with diabetic nephropathy in type 1 diabetic patients

2007 ◽  
Vol 33 (1) ◽  
pp. 37-43 ◽  
Author(s):  
S. Hadjadj ◽  
F. Duengler ◽  
F. Torremocha ◽  
G. Faure-Gerard ◽  
F. Bridoux ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Diabetic Patients ◽  
Maternal History ◽  
History Of ◽  
Type 1 Diabetic Patients

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.

scholarly journals Arg913Gln variation of SLC12A3 gene is associated with diabetic nephropathy in type 2 diabetes and Gitelman syndrome: a systematic review

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Eduardo De la Cruz-Cano ◽  
Cristina del C. Jiménez-González ◽  
Vicente Morales-García ◽  
Conny Pineda-Pérez ◽  
Juan G. Tejas-Juárez ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Gitelman Syndrome ◽  
Slc12a3 Gene ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Diabetic nephropathy is a global common cause of chronic kidney disease and end-stage renal disease. A lot of research has been conducted in biomedical sciences, which has enhanced understanding of the pathophysiology of diabetic nephropathy and has expanded the potential available therapies. An increasing number of evidence suggests that genetic alterations play a major role in development and progression of diabetic nephropathy. This systematic review was focused on searching an association between Arg913Gln variation in SLC12A3 gene with diabetic nephropathy in individuals with Type 2 Diabetes and Gitelman Syndrome. Methods An extensive systematic review of the literature was completed using PubMed, EBSCO and Cochrane Library, from their inception to January 2018. The PRISMA guidelines were followed and the search strategy ensured that all possible studies were identified to compile the review. Inclusion criteria for this review were: 1) Studies that analyzed the SLC12A3 gene in individuals with Type 2 Diabetes and Gitelman Syndrome. 2) Use of at least one analysis investigating the association between the Arg913Gln variation of SLC12A3 gene with diabetic nephropathy. 3) Use of a case–control or follow-up design. 4) Investigation of type 2 diabetes mellitus in individuals with Gitelman’s syndrome, with a history of diabetic nephropathy. Results The included studies comprised 2106 individuals with diabetic nephropathy. This review shows a significant genetic association in most studies in the Arg913Gln variation of SLC12A3 gene with the diabetic nephropathy, pointing out that the mutations of this gene could be a key predictor of end-stage renal disease. Conclusions The results showed in this systematic review contribute to better understanding of the association between the Arg913Gln variation of SLC12A3 gene with the pathogenesis of diabetic nephropathy in individuals with T2DM and GS.

scholarly journals The Role of Transforming Growth Factor-Beta in Diabetic Nephropathy

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Karina Braga Gomes ◽  
Kathryna Fontana Rodrigues ◽  
Ana Paula Fernandes
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Low Grade ◽  
Anti Inflammatory

Several studies have demonstrated that chronic and low-grade inflammation is closely linked to type 2 diabetes mellitus. The associated mechanisms are related to synthesis and release of proinflammatory and anti-inflammatory cytokines, mainly by the adipose tissue. Moreover, there are evidences that cytokines and adhesion molecules are important for development of diabetic nephropathy. Among the cytokines associated with inflammatory responses in type 2 diabetes mellitus, the transforming growth factor-β (TGF-β) has been recognized as a central player in the diabetic nephropathy being involved in the development of glomerulosclerosis and interstitial fibrosis, as observed in the course of end-stage renal disease. Although TGF-β1 is classically an anti-inflammatory immune mediator it has been shown that in the presence of IL-6, which increases before the onset of T2D, TGF-β1 favors the differentiation of T helper 17 (Th17) cells that are activated in many pro-inflammatory conditions. Since TGF-β1 mRNA and consequently serum TGF-β1 levels are under genetic control, this review aims to discuss the relationship of TGF-β1 levels and polymorphisms in the development of nephropathy in type 2 diabetes mellitus.

scholarly journals Effect of MTHFR C677T genotype on survival in type 2 diabetes patients with end-stage diabetic nephropathy

2006 ◽  
Vol 22 (1) ◽  
pp. 154-162 ◽  
Author(s):  
C. A. Boger ◽  
M. Stubanus ◽  
T. Haak ◽  
A. K. Gotz ◽  
J. Christ ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Mthfr C677t ◽  
End Stage ◽  
Diabetes Patients

scholarly journals Urinary complement proteins and risk of end-stage renal disease: quantitative urinary proteomics in patients with type 2 diabetes and biopsy-proven diabetic nephropathy

2021 ◽  
Author(s):  
L. Zhao ◽  
Y. Zhang ◽  
F. Liu ◽  
H. Yang ◽  
Y. Zhong ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Renal Outcome ◽  
Complement Proteins ◽  
Stage Renal Disease ◽  
End Stage ◽  
Egfr Decline

Abstract Purpose To investigate the association between urinary complement proteins and renal outcome in biopsy-proven diabetic nephropathy (DN). Methods Untargeted proteomic and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses and targeted proteomic analysis using parallel reaction-monitoring (PRM)-mass spectrometry was performed to determine the abundance of urinary complement proteins in healthy controls, type 2 diabetes mellitus (T2DM) patients, and patients with T2DM and biopsy-proven DN. The abundance of each urinary complement protein was individually included in Cox proportional hazards models for predicting progression to end-stage renal disease (ESRD). Results Untargeted proteomic and functional analysis using the KEGG showed that differentially expressed urinary proteins were primarily associated with the complement and coagulation cascades. Subsequent urinary complement proteins quantification using PRM showed that urinary abundances of C3, C9, and complement factor H (CFAH) correlated negatively with annual estimated glomerular filtration rate (eGFR) decline, while urinary abundances of C5, decay-accelerating factor (DAF), and CD59 correlated positively with annual rate of eGFR decline. Furthermore, higher urinary abundance of CFAH and lower urinary abundance of DAF were independently associated with greater risk of progression to ESRD. Urinary abundance of CFAH and DAF had a larger area under the curve (AUC) than that of eGFR, proteinuria, or any pathological parameter. Moreover, the model that included CFAH or DAF had a larger AUC than that with only clinical or pathological parameters. Conclusion Urinary abundance of complement proteins was significantly associated with ESRD in patients with T2DM and biopsy-proven DN, indicating that therapeutically targeting the complement pathway may alleviate progression of DN.

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