Meta-Analysis and Bioinformatics Detection of Susceptibility Genes in Diabetic Nephropathy

The latest meta-analysis of genome-wide linkage studies (GWLS) identified nine cytogenetic locations suggestive of a linkage with diabetic nephropathy (DN) due to type 1 diabetes mellitus (T1DM) and seven locations due to type 2 diabetes mellitus (T2DM). In order to gain biological insight about the functional role of the genes located in these regions and to prioritize the most significant genetic loci for further research, we conducted a gene ontology analysis with an over representation test for the functional annotation of the protein coding genes. Protein analysis through evolutionary relationships (PANTHER) version 16.0 software and Cytoscape with the relevant plugins were used for the gene ontology analysis, and the overrepresentation test and STRING database were used for the construction of the protein network. The findings of the over-representation test highlight the contribution of immune related molecules like immunoglobulins, cytokines, and chemokines with regard to the most overrepresented protein classes, whereas the most enriched signaling pathways include the VEGF signaling pathway, the Cadherin pathway, the Wnt pathway, the angiogenesis pathway, the p38 MAPK pathway, and the EGF receptor signaling pathway. The common section of T1DM and T2DM results include the significant over representation of immune related molecules, and the Cadherin and Wnt signaling pathways that could constitute potential therapeutic targets for the treatment of DN, irrespective of the type of diabetes.

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Proanthocyanidins Protect Against Cadmium-Induced Diabetic Nephropathy Through p38 MAPK and Keap1/Nrf2 Signaling Pathways

Frontiers in Pharmacology ◽

10.3389/fphar.2021.801048 ◽

2022 ◽

Vol 12 ◽

Author(s):

Pin Gong ◽

Peipei Wang ◽

Sihui Pi ◽

Yuxi Guo ◽

Shuya Pei ◽

...

Keyword(s):

Diabetes Mellitus ◽

Diabetic Nephropathy ◽

Signaling Pathways ◽

Signaling Pathway ◽

P38 Mapk ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Protective Mechanism ◽

Protective Effects ◽

Antioxidative Status

Diabetic nephropathy (DN) is one of the most devastating complications of diabetes mellitus. Although cadmium (Cd) exposure might be involved in the pathogenesis of DN, the underlying mechanism is still unclear. In this study, we explored the protective effects and possible mechanism of proanthocyanidins (OPC) from grape seed using a mouse model of Cd-induced DN. The successful establishment of this model was verified by analyzing the physiological and biochemical indices of mice, including their body weight and tissue ratio; levels of blood glucose, creatinine, microalbumin, total cholesterol, triglycerides, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol; and was based on histopathological examination. Oxidative-antioxidative status, elemental analysis, and key signaling pathway analysis were performed to explore the possible protective mechanism of OPC. The protective effects of OPC and its possible mechanism in preventing the progression of DN were investigated using a multidimensional approach, including its ability in regulating oxidative-antioxidative status (lipid peroxidation, protein carbonyl, superoxide dismutase, and glutathione GST, GSH-Px), metal-binding ability (Cd levels in the kidneys and urine and MT content) and mediation of essential elements (Zn, Ca, Cu, and Fe levels in the kidneys), and activation of the p38 MAPK and Keap1/Nrf2 signaling pathways. OPC exhibited a significant renoprotective effect, attributed to the metal-chelating ability, anti-oxidative effect, and mediation of oxidative stress-related signaling pathway. These results highlight the potential of OPC in preventing or treating DN in humans and suggest the dietary intake of grapes, which are rich in polyphenols, for the prevention of type 2 diabetes mellitus and its complications.

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Clinical Utility of Serum Cystatin C in Predicting Diabetic Nephropathy Among Patients with Diabetes Mellitus: a Meta-Analysis

Kidney & Blood Pressure Research ◽

10.1159/000452593 ◽

2016 ◽

Vol 41 (6) ◽

pp. 919-928 ◽

Cited By ~ 11

Author(s):

Baoqin Zhou ◽

Honghong Zou ◽

Gaosi Xu

Keyword(s):

Diabetes Mellitus ◽

Diabetic Nephropathy ◽

Cystatin C ◽

Clinical Utility ◽

Meta Analysis ◽

Serum Cystatin C ◽

Serum Cystatin ◽

Patients With Diabetes

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Association of Helicobacter pylori infection with diabetes mellitus and diabetic nephropathy: A meta-analysis of 39 studies involving more than 20,000 participants

Scandinavian Journal of Infectious Diseases ◽

10.3109/00365548.2013.844351 ◽

2013 ◽

Vol 45 (12) ◽

pp. 930-938 ◽

Cited By ~ 22

Author(s):

Feng Wang ◽

Juan Liu ◽

Zongshun Lv

Keyword(s):

Diabetes Mellitus ◽

Helicobacter Pylori ◽

Diabetic Nephropathy ◽

Meta Analysis ◽

Helicobacter Pylori Infection

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Islet Transplantation Reverses Podocyte Injury in Diabetic Nephropathy or Induced by High Glucose via Inhibiting RhoA/ROCK/NF-κB Signaling Pathway

Journal of Diabetes Research ◽

10.1155/2021/9570405 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Chongchu Huang ◽

Yi Zhou ◽

Hongjian Huang ◽

Yushu Zheng ◽

Lijun Kong ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Signaling Pathways ◽

Signaling Pathway ◽

Islet Transplantation ◽

High Glucose ◽

Islet Cells ◽

Inflammatory Factors ◽

Efficacy Evaluation ◽

Podocyte Injury ◽

Expression Levels

Objective. Abnormal signaling pathways play a crucial role in the mechanisms of podocyte injury in diabetic nephropathy. They also affect the recovery of podocytes after islet transplantation (IT). However, the specific signaling abnormalities that affect the therapeutic effect of IT on podocytes remains unclear. The purpose of this study was to assess whether the RhoA/ROCK/NF-κB signaling pathway is related to podocyte restoration after IT. Methods. A mouse model of diabetic nephropathy was established in vivo using streptozotocin. The mice were then subsequently reared for 4 weeks after islet transplantation to determine the effect of IT. Islet cells, CCG-1423 (RhoA Inhibitor), and fasudil (ROCK inhibitor) were then cocultured with podocytes in vitro to assess their protective effects on podocyte injury induced by high glucose (HG). Protein expression levels of RhoA, ROCK1, synaptopodin, IL-6, and MCP-1 in kidney tissues were then measured using immunohistochemistry and Western blotting techniques. Results. Islet transplantation reduced the expression levels of RhoA/ROCK1 and that of related inflammatory factors such as IL-6 and MCP-1 in the kidney podocytes of diabetic nephropathy. In the same line, islet cells reduced the expression of RhoA, ROCK1, and pp65 in immortalized podocytes under high glucose (35.0 mmol/L glucose) conditions. Conclusions. Islet transplantation can reverse podocyte injury in diabetes nephropathy by inhibiting the RhoA/ROCK1 signaling pathway. Islet cells have a strong protective effect on podocytes treated with high glucose (35.0 mmol/L glucose). Discovery of signaling pathways affecting podocyte recovery is helpful for individualized efficacy evaluation and targeted therapy of islet transplantation patients.

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Urinary N-Acetyl-β-d-glucosaminidase (uNAG) as an Indicative Biomarker of Early Diabetic Nephropathy in Patients with Diabetes Mellitus (T1DM, T2DM): A Systematic Review and Meta-Analysis

Diabetology ◽

10.3390/diabetology2040025 ◽

2021 ◽

Vol 2 (4) ◽

pp. 272-285

Author(s):

Arlinda R. Driza ◽

Georgia V. Kapoula ◽

Pantelis G. Bagos

Keyword(s):

Diabetes Mellitus ◽

Systematic Review ◽

Diabetic Nephropathy ◽

Meta Analysis ◽

Area Under The Curve ◽

Diabetic Patients ◽

Pool Data ◽

Patients With Diabetes ◽

Pubmed Search ◽

Renal Tubular

Diabetic nephropathy (DN) is the main cause of chronic kidney disease in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Renal tubular lysosomal enzyme activities like N-acetyl-β-d-glucosaminidase (NAG) have been shown to increase in patients developing DN. The aim of this systematic review and meta-analysis is to evaluate the diagnostic accuracy of NAG, as a preventional biomarker in the early stages of DN in patients with diabetes mellitus. Two impartial reviewers conducted a complete PubMed search until July 2021. A 2 × 2 contingency table was created for each trial and sensitivity and specificity were estimated using a bivariate random effects model. To pool data and estimate the area under the curve (AUC), the hierarchical summary ROC (hsROC) approach was utilized. Deek’s test was used to estimate publication bias. The meta-analysis included 21 studies that evaluated 2783 patients with T1DM and T2DM, as well as 673 healthy individuals. The AUC of urinary NAG (uNAG) ranged from 0.69 (95% CI: 0.65–0.73) to 0.89 (95% CI: 0.86–0.92). According to the results, NAG in urine can be considered as a potential and effective biomarker for predicting DN in diabetic patients (T1DM, T2DM).

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Serum Irisin and Diabetic Nephropathy in Patients with Diabetes Mellitus

Hormone and Metabolic Research ◽

10.1055/a-1676-4118 ◽

2021 ◽

Vol 53 (12) ◽

pp. 825-825

Author(s):

Tomoyuki Kawada

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Diabetic Nephropathy ◽

Meta Analysis ◽

Infiltration Rate ◽

Fundamental Relationship ◽

Patients With Diabetes ◽

The Mean

Dear Editor,I read the article by Wang et al., who conducted a meta-analysis to investigate the association between serum irisin levels and diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM) 1. The mean serum irisin level in T2DM patients with microalbuminuria was significantly lower than that in T2DM patients with normoalbuminuria. In addition, the mean serum irisin level in T2DM patients with macroalbuminuria was significantly lower than that in T2DM patients with microalbuminuria. Furthermore, the mean serum irisin level in T2DM patients with estimated glomerular infiltration rate (eGFR)<60 ml/min 1.73 m2 was significantly lower than that in T2DM patients with eGFR≥60 ml/min 1.73 m2. The authors concluded that decreased serum irisin level was associated with albuminuria and reduced eGFR in T2DM patients. DN was significantly related to decreased serum irisin level in T2DM patients with dose-response manner. Progression of DN may be considered as advanced DM status, and serum irisin level would reflect glucose intolerance via insulin resistance. I have a comment about their study with special reference to the fundamental relationship between the types of DM and serum irisin levels.

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Association Between Serum Irisin and Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis

Hormone and Metabolic Research ◽

10.1055/a-1475-4444 ◽

2021 ◽

Vol 53 (05) ◽

pp. 293-300

Author(s):

Rui Wang ◽

Hongyan Liu

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Diabetic Nephropathy ◽

Meta Analysis ◽

Case Control ◽

Case Control Studies ◽

Lower Serum ◽

Matched Case

AbstractIrisin, an emerging adipokine, has been involved in the pathogenesis of type 2 diabetes mellitus (T2DM). However, previous studies evaluating the association between irisin and diabetic nephropathy (DN) showed inconsistent results. We performed a meta-analysis to evaluate the above association. Matched case-control studies evaluating the difference of serum irisin between T2DM patients with and without DN were identified via systematic search of PubMed, Embase, Cochranes’ Library, China National Knowledge Infrastructure, and WanFang databases from inception to December 5, 2020. A random-effects model or a fixed-effects model was used to pool the results according to the heterogeneity. Overall, thirteen matched case-control studies including 1735 T2DM patients were included. Results of meta-analysis showed that compared to T2DM patients with normoalbuminuria, those with microalbuminuria [10 studies, standard mean difference (SMD): 1.12, 95% confidence interval (CI): 0.48–1.77, p<0.001; I2=94%] and macroalbuminuria (10 studies, SMD: 1.86, 95% CI: 0.93–2.79, p<0.001; I2=97%) had significantly lower serum irisin. Besides, the serum level of irisin was significantly lower in T2DM patients with macroalbuminuria than those with microalbuminuria (10 studies, SMD: 0.91, 95% CI: 0.44–1.38, p<0.001; I2=90%). In addition, patients with estimated glomerular infiltration rate (eGFR)<60 ml/min 1.73 m2 had lower serum irisin compared to those with eGFR≥60 ml/min 1.73 m2 (4 studies, SMD: 0.89, 95% CI: 0.32–1.46, p=0.002; I2=91%). In conclusion, serum irisin may be associated with albuminuria and reduced eGFR in T2DM patients.

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