scholarly journals Extracellular vesicle-derived AEBP1 mRNA as a novel candidate biomarker for diabetic kidney disease

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yiying Tao ◽  
Xing Wei ◽  
Yue Yue ◽  
Jiaxin Wang ◽  
Jianzhong Li ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Kidney Tissue ◽  
Extracellular Vesicle ◽  
Clinical Parameter ◽  
Diagnostic Efficacy ◽  
Diabetic Kidney ◽  
Efficacy Assessment ◽  
Novel Biomarkers ◽  
And Control

Abstract Background A novel and improved methodology is still required for the diagnosis of diabetic kidney disease (DKD). The aim of the present study was to identify novel biomarkers using extracellular vesicle (EV)-derived mRNA based on kidney tissue microarray data. Methods Candidate genes were identified by intersecting the differentially expressed genes (DEGs) and eGFR-correlated genes using the GEO datasets GSE30528 and GSE96804, followed by clinical parameter correlation and diagnostic efficacy assessment. Results Fifteen intersecting genes, including 8 positively correlated genes, B3GALT2, CDH10, MIR3916, NELL1, OCLM, PRKAR2B, TREM1 and USP46, and 7 negatively correlated genes, AEBP1, CDH6, HSD17B2, LUM, MS4A4A, PTN and RASSF9, were confirmed. The expression level assessment results revealed significantly increased levels of AEBP1 in DKD-derived EVs compared to those in T2DM and control EVs. Correlation analysis revealed that AEBP1 levels were positively correlated with Cr, 24-h urine protein and serum CYC and negatively correlated with eGFR and LDL, and good diagnostic efficacy for DKD was also found using AEBP1 levels to differentiate DKD patients from T2DM patients or controls. Conclusions Our results confirmed that the AEBP1 level from plasma EVs could differentiate DKD patients from T2DM patients and control subjects and was a good indication of the function of multiple critical clinical parameters. The AEBP1 level of EVs may serve as a novel and efficacious biomarker for DKD diagnosis.

scholarly journals A hyaluronan synthesis inhibitor delays progression of diabetic kidney disease in a mouse experimental model

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0004642020
Author(s):  
Guillermo Selman ◽  
Laisel Martinez ◽  
Andrea Lightle ◽  
Alejandra Aguilar ◽  
Daniel Woltmann ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Plasma Glucose ◽  
Diabetic Kidney Disease ◽  
Control Diet ◽  
Experimental Period ◽  
Glomerular Injury ◽  
Synthesis Inhibitor ◽  
Diabetic Kidney ◽  
Injury Index ◽  
And Control

Background: The role of hyaluronan (HA) in the development and progression of diabetic kidney disease (DKD), as well as the precise mechanisms and consequences of HA involvement in this pathology are still to be clarified. Methods: In this study, we assayed the effects of the HA synthesis inhibitor 4-methylumbelliferone (4-MU) on the development of DKD. Diabetic type 2 model mice (eNOS-/- C57BLKS/Jdb) were fed artificial diets containing 5% 4-MU or not for 9 weeks. Plasma glucose, glomerular filtration rate (GFR), albumin to creatinine ratio (ACR), and biomarkers of kidney function and systemic inflammation were measured at baseline and after treatment. Diabetic nephropathy was further characterized in treated and control mice by histopathology. Results: Treated animals consumed a daily dose of approximately 6.2 g of 4-MU per kg of body weight. At the end of the experimental period, the 4-MU supplemented diet resulted in a significant decrease in non-fasting plasma glucose (516 [interquartile range 378-1170] vs. 1149 [875.8-1287] mg/dL, P=0.050) and a trend toward lower HA kidney content (5.6 ± 1.5 vs. 8.8 ± 3.1 ng/mg of kidney weight, P=0.070) compared to the control diet, respectively. Diabetic animals treated with 4-MU showed significantly higher GFR and lower urine ACR and plasma cystatin C levels than diabetic controls. Independent histological assessment of DKD also demonstrated a significant decrease in mesangial expansion score and glomerular injury index in 4-MU-treated mice compared to controls. Plasma glucose showed a strong correlation with kidney HA levels (r=0.66, P=0.0098). Both total hyaluronan (r=0.76, P=0.0071) and low-molecular-weight hyaluronan content (r=0.64, P=0.036) in the kidneys correlated with urine ACR in mice. Conclusion: These results show that the hyaluronan synthesis inhibitor 4-MU effectively slowed the progression of DKD and constitutes a potential new therapeutic approach to treat DKD.

Urinary exosomal microRNA panel unravels novel biomarkers for diagnosis of type 2 diabetic kidney disease

2016 ◽  
Vol 30 (8) ◽  
pp. 1585-1592 ◽  
Author(s):  
Sanaa Eissa ◽  
Marwa Matboli ◽  
Rowaida Aboushahba ◽  
Miram M. Bekhet ◽  
Yasser Soliman
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Novel Biomarkers ◽  
Exosomal Microrna ◽  
Type 2 Diabetic

scholarly journals Correlations between SIRT1 gene polymorphisms and diabetic kidney disease

2018 ◽  
Vol 5 (6) ◽  
pp. 171871 ◽  
Author(s):  
Xin-Ge Yue ◽  
Zai-Gang Yang ◽  
Yue Zhang ◽  
Gui-Jun Qin ◽  
Fei Liu
Keyword(s):  
Kidney Disease ◽  
Gene Polymorphisms ◽  
Diabetic Kidney Disease ◽  
Susceptibility Gene ◽  
Albumin Excretion Rate ◽  
Control Group ◽  
Diabetic Kidney ◽  
Significant Difference ◽  
Sirt1 Gene ◽  
And Control

To investigate the correlations between SIRT1 gene polymorphisms and diabetic kidney disease (DKD). There were 150 patients with DKD in the observation group (urinary albumin excretion rate (UAER) ≥ 300 mg 24 h −1 ), and 160 patients with a more than 10 year history of type 2 diabetes but without retinopathy and DKD (UAER < 30 mg 24 h −1 ) in the control group. Genotypes of three tagged single-nucleotide polymorphism loci (rs3818292, rs4746720 and rs10823108) in the SIRT1 gene in the two groups were detected. Risks of DKD for patients with the GG and GG + AG genotype in the rs10823108 locus of the SIRT1 gene were 2.96 and 2.92 times higher than that for AA genotype carriers, respectively. The risk of DKD for patients with the GG genotype in the rs3818292 locus was 0.23 times and 0.21 times higher than that for AA and for AA + AG genotype carriers, respectively, and the risk of DKD for patients with allele G was 0.66 times higher than that for allele A carriers. There was no significant difference in genotype frequency of rs4746720 locus gene polymorphisms between the observation and control groups. The SIRT1 gene is a genetic susceptibility gene of DKD. Mutation genotype GG and GG + AG in the rs10823108 locus can increase the risk of DKD. Mutation genotype GG and allele G in the rs3818292 locus can decrease the risk of DKD.

scholarly journals Urinary Exosomal MicroRNA Profiling in Incipient Type 2 Diabetic Kidney Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Yijun Xie ◽  
Yijie Jia ◽  
Xie Cuihua ◽  
Fang Hu ◽  
Meng Xue ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Early Stage ◽  
Strong Predictor ◽  
Differentially Expressed ◽  
Diabetic Kidney ◽  
Reverse Transcription Pcr ◽  
Novel Biomarkers ◽  
Renal Failure Fluid

Background. Albuminuria is an early sign but not a strong predictor of diabetic kidney disease (DKD). Owing to their high stability, urinary exosomal miRNAs can be useful predictors of the progression of early-stage DKD to renal failure; fluid biopsies are ideal for detecting abnormalities in these miRNAs. The aim of this study was to identify novel differentially expressed miRNAs as urine biomarkers for type 2 DKD by comparing between patients of type 2 diabetes (T2D) with and without macroalbuminuria. Methods. Ten patients with T2D, including five who had no renal disease and five with macroalbuminuria (DKD G1-2A3), were selected for this study. Exosome- (UExo-) derived miRNA profiles were used to identify candidate biomarkers, a subset of which was verified using quantitative reverse transcription PCR. Results. A total of 496 UExo-derived miRNA species were found to be differentially expressed (>2-fold) in patients with DKD, compared to those with T2D. A validation analysis revealed that three miRNAs (miR-362-3p, miR-877-3p, and miR-150-5p) were upregulated and one (miR-15a-5p) was downregulated. These miRNAs might regulate DKD through p53, mTOR, and AMPK pathways. Conclusions. In conclusion, UExo-derived miRNAs were altered in type 2 DKD. MiR-362-3p, miR-877-3p, miR-150-5p, and miR-15a-5p might be novel biomarkers for incipient DKD.

scholarly journals FcER1: A Novel Molecule Implicated in the Progression of Human Diabetic Kidney Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Swastika Sur ◽  
Mark Nguyen ◽  
Patrick Boada ◽  
Tara K. Sigdel ◽  
Hans Sollinger ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Target Genes ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Rational Drug Design ◽  
Transcriptional Analysis ◽  
Peripheral Blood Mononuclear ◽  
Tissue Samples ◽  
Diabetic Kidney

Diabetic kidney disease (DKD) is a key microvascular complication of diabetes, with few therapies for targeting renal disease pathogenesis and progression. We performed transcriptional and protein studies on 103 unique blood and kidney tissue samples from patients with and without diabetes to understand the pathophysiology of DKD injury and its progression. The study was based on the use of 3 unique patient cohorts: peripheral blood mononuclear cell (PBMC) transcriptional studies were conducted on 30 patients with DKD with advancing kidney injury; Gene Expression Omnibus (GEO) data was downloaded, containing transcriptional measures from 51 microdissected glomerulous from patients with DKD. Additionally, 12 independent kidney tissue sections from patients with or without DKD were used for validation of target genes in diabetic kidney injury by kidney tissue immunohistochemistry and immunofluorescence. PBMC DKD transcriptional analysis, identified 853 genes (p &lt; 0.05) with increasing expression with progression of albuminuria and kidney injury in patients with diabetes. GEO data was downloaded, normalized, and analyzed for significantly changed genes. Of the 325 significantly up regulated genes in DKD glomerulous (p &lt; 0.05), 28 overlapped in PBMC and diabetic kidney, with perturbed FcER1 signaling as a significantly enriched canonical pathway. FcER1 was validated to be significantly increased in advanced DKD, where it was also seen to be specifically co-expressed in the kidney biopsy with tissue mast cells. In conclusion, we demonstrate how leveraging public and private human transcriptional datasets can discover and validate innate immunity and inflammation as key mechanistic pathways in DKD progression, and uncover FcER1 as a putative new DKD target for rational drug design.

scholarly journals The potential effects of dietary flavones on diabetic nephropathy; a review of mechanisms

2020 ◽  
Vol 9 (2) ◽  
pp. e09-e09
Author(s):  
Lida Menati ◽  
Amirhosein Meisami ◽  
Mitra Zarebavani
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Kidney Tissue ◽  
Experimental Models ◽  
Antioxidant Systems ◽  
Protective Effects ◽  
Diabetic Kidney ◽  
Natural Agents ◽  
Patients With Diabetes

Diabetes as a chronic metabolic disorder affects the worldwide population with high incidence of morbidity and mortality. Different complications such as nephropathy, neuropathy, ocular diseases, and cardiovascular disease are common in patients with diabetes that threaten the patient’s lifestyle. Diabetic nephropathy (DN) usually is related to some major structural alterations in the kidney which characterized by generation of toxic reactive oxygen species (ROS) or inhibition of antioxidant systems in kidney tissue. Different natural agents have been introduced to be used as a complementary treatment to prevent diabetic kidney disease. Flavones (apigenin, luteolin, nobiletin and chrysin) as a subgroup of flavonoids are natural occurring substances which have several pharmacological activates, including antioxidant, antiapoptotic, anti-inflammatory, and anti-tumor efficacy. Recent evidence indicated that flavones may be effective for prevention and treatment of diabetes complications in experimental models. The present study was designed to review the relationship between flavones administration and diabetes and diabetic kidney disease by focusing on the possible molecular pathway. The findings indicate that flavones have protective effects against diabetic kidney disease by modulation of different pathways related to oxidative stress, inflammation, and apoptosis in animal models. Therefore, more clinical investigations are suggested to be conducted to find the protective effects of flavones in patients with diabetes.

scholarly journals Urinary exosomal microRNA panel unravels novel biomarkers for diagnosis of type 2 diabetic kidney disease

QJM ◽  
2018 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
S Eissa ◽  
M Matboli ◽  
R Aboushahba ◽  
M M Bekhet ◽  
Y Soliman
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Novel Biomarkers ◽  
Exosomal Microrna ◽  
Type 2 Diabetic

In Diabetic Kidney Disease Urinary Exosomes Better Represent Kidney Specific Protein Alterations Than Whole Urine

2015 ◽  
Vol 42 (6) ◽  
pp. 418-424 ◽  
Author(s):  
Krishnamurthy P. Gudehithlu ◽  
Ignacio Garcia-Gomez ◽  
Jane Vernik ◽  
Carolyn Brecklin ◽  
Mark Kraus ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Structural Changes ◽  
Sandwich Elisa ◽  
Kidney Tissue ◽  
Protein Markers ◽  
Gelatinase Activity ◽  
Diabetic Kidney ◽  
Urinary Exosomes ◽  
Whole Urine

Background: Predicting or diagnosing underlying kidney disease by analyzing whole urine remains the mainstay of nephrology practice. However, whole urine is a poor compartment to assess many structural changes in the kidney because whole urine contains only a few proteins derived from the kidney itself. Urinary exosomes, on the other hand, which are derived from the kidney, contain proteins secreted by the kidney. We experimentally tested the hypothesis that ‘urinary exosomes more faithfully represent changes in the kidney tissue than whole urine'. A direct comparison between whole urine and urine exosomal levels of two chosen kidney disease markers, gelatinase and ceruloplasmin, was carried out on diabetic kidney disease patients. Methods: Urinary exosomes were separated from whole urine by sequential centrifugation including ultra-centrifugation. Gelatinase activity was measured using fluorosceinated gelatin as the substrate, and ceruloplasmin was measured by sandwich ELISA. A few kidney specimens from patients biopsied for atypical features were histochemically stained for validation of the biochemical results. Results: We found that changes in both, gelatinase (decreased activity) and ceruloplasmin (increased levels), in the urinary exosomes of diabetic kidney patients were in agreement with the alterations of these two proteins in the kidney tissue. In contrast, the levels of these two proteins in whole urine were highly variable and did not correlate with levels in the diabetic kidney tissue. Conclusion: In conclusion, these results confirmed our hypothesis that protein markers in urinary exosomes better reflected the underlying protein changes in the kidney than in whole urine samples.

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