Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy

Lee, Wen‐Chin; Li, Lung-Chih; Ng, Hwee-Yeong; Lin, Pei-Ting; Chiou, Terry Ting-Yu; Kuo, Wei-Hung; Lee, Chien-Te

doi:10.3390/jcm9041220

Cited by 19 publications

(17 citation statements)

References 42 publications

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“…MiR-133a can target the Krueppel-like factor 15 (Klf15) mRNA, inhibiting this transcriptional factor, which is an enhancer of GLUT4 expression, thus leading to the reduction in GLUT4 expression and in insulin stimulated glucose uptake ( 5 ). MiR-133a not only showed differential expression in blood level of T2DM, but also in tissue levels of T2DM complications, such as kidney, heart, sciatic nerve, and skeletal muscle ( 26 – 29 ). MiR-133a-2 rs13040413 variant could also increase levels of miR-133a ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

Association of Genetic Polymorphisms in MicroRNAs With Type 2 Diabetes Mellitus in a Chinese Population

et al. 2021

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IntroductionMicroRNAs (miRNA) involved in the insulin signaling pathways deeply affect the pathogenesis of T2DM. The aim of this study was to assess the association between single nucleotide polymorphisms (SNP) of the related miRNAs (let-7f rs10877887, let-7a-1 rs13293512, miR-133a-1 rs8089787, miR-133a-2 rs13040413, and miR-27a rs895819) and susceptibility to type 2 diabetes mellitus (T2DM), and its possible mechanisms.MethodsFive SNPs in miRNAs (let-7f rs10877887, let-7a-1 rs13293512, miR-133a-1 rs8089787, miR-133a-2 rs13040413, and miR-27a rs895819) involved in the insulin signaling pathways were selected and genotyped in a case-control study that enrolled 371 T2DM patients and 381 non-diabetic controls. The individual SNP association analyses, interaction analyses of SNP-SNP, SNP-environmental factors were performed. The effect the risk-associated polymorphism on regulating its mature miRNA expression was also evaluated.ResultsIn overall analyses, miR-133a-2 rs13040413 and let-7a-1 rs13293512 were related to the susceptibility to T2DM. In stratified analyses, miR-133a-2 rs13040413, let-7a-1 rs13293512 and miR-27a rs895819 showed associations with T2DM in the age ≥ 60 years subgroup. Moreover, let-7a-1 rs13293512 and miR-27a rs895819 showed associations with T2DM in male subgroup. In SNP-environmental factors interaction analyses, there were interaction effects of miR-133a-2 rs13040413 with dyslipidemia, let-7a-1 rs13293512 with smoking, and let-7a-1 rs13293512 with dyslipidemia on T2DM. In SNP-SNP interaction analyses, there were also interaction effects of miR-133a-1 rs8089787 with let-7a-1 rs13293512, and miR-133a-1 rs8089787 with let-7f rs10877887 on T2DM. Furthermore, for miR-133a-2 rs13040413, the variant T allele showed a trend toward decreased miR-133a expression in comparison with the wild C allele. For let-7a-1 rs13293512, the variant C allele expressed a lower let-7a compared to the wild T allele.ConclusionMiRNAs polymorphisms involved in the insulin signaling pathways and the interaction effects of SNP-SNP, SNP-environmental factors were related to T2DM susceptibility in a Chinese population.

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Section: Discussionmentioning

confidence: 99%

Association of Genetic Polymorphisms in MicroRNAs With Type 2 Diabetes Mellitus in a Chinese Population

et al. 2021

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“…In this instance, we suggested new pathways in the pathogenesis of nephropathy in type 2 diabetes mellitus and consequently provided novel biomarkers as predictors for early detection, accurate diagnosis, and targeted therapy of DN. Although several previous studies had focused on the profile of mRNAs and microRNAs in the urine exosomes as well as circulating exosomal microRNAs in DN [ 9 , 17 , 18 , 23 – 31 ], to our knowledge so far, this is the first study on the mRNAs specifically in the blood exosomes of DN patients. One of the advantages of blood exosomes over urine exosomes is that the concentration of urine exosomes and subsequently its overall contents were affected by food uptake and urine volume while blood exosomal compositions did not depend on these factors [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

WT1 and ACE mRNAs of blood extracellular vesicle as biomarkers of diabetic nephropathy

et al. 2021

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Background Diabetic nephropathy (DN) has an increasing global prevalence with excessive health expenditure and burden. Exosomal mRNAs regulate intercellular communications and participate in the pathogenesis of various disorders like DN. This study aimed to assess the expression levels of ACE, ELMO1, and WT1 mRNAs in the blood extracellular vesicles (EVs) of DN patients and diabetic patients without nephropathy (DM group) in comparison to healthy controls and investigate their correlations with the severity of DN. Methods The performed investigation is a cross-sectional study of 256 participants including 103 DN patients, 100 DM patients, and 53 healthy controls. The quantification of WT1, ACE, and ELMO1 mRNAs in the blood EVs were executed using qRT-PCR. The ROC analysis was performed to determine the diagnostic accuracy of mRNAs. Results DN patients had significantly higher expressed WT1 mRNA (1.70-fold change) and lower expressed ACE mRNA (0.55-fold change) in the blood EVs compared to DM patients and controls. ELMO1 mRNA was not expressed in EVs of any groups. A positive correlation between WT1 mRNA level and urine Alb/Cr ratio (r = 0.602, p < 0.001) and a negative correlation between ACE mRNA expression and urine Alb/Cr ratio within DN patients (r = − 0.474, p < 0.001) was identified. The accuracy of WT1 mRNA and 1/ACE mRNA for predicting incipient DN was 0.63 (95% CI 0.55, 0.72) and 0.62 (95% CI 0.54, 0.71), and for predicting overt DN was 0.83 (95% CI 0.74, 0.92) and 0.75 (95% CI 0.66, 0.83), respectively. Conclusions WT1 and ACE mRNAs level in blood EVs were predictors for early diagnosis of DN therefore their quantifications might be used to determine the severity of albuminuria and glomerular injuries.

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“…Diabetic nephropathy may be improved by antioxidant action and thus decreased ROS production (28). These studies further confirm that the PI3K-Akt signaling pathway plays a critical role in the progression of DN (29,30).…”

Section: Discussionmentioning

confidence: 55%

Identification of Hub Genes in Diabetic Nephropathy by an Integrated Bioinformatic Analysis

Chen

Qiu

2021

Preprint

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BackgroundDiabetic nephropathy (DN) is a progressive kidney disease caused by damage to the capillaries in the kidneys' glomeruli. The dysregulation of genes plays a significant role in the progression of DN. MethodsIn the present study, gene expression profiles were analyzed to identify the key genes and pathways involved in DN. Gene expression profiles of 9 patients with DN and 11 normal subjects were downloaded from the Gene Expression Omnibus (GEO) database. Subsequently, differentially expressed genes (DEGs) were identified and subjected to functional enrichment analysis. In addition, protein-protein interaction (PPI) networks were established and hub genes were identified. ResultsAs a result, a total of 424 DEGs were identified (113 were upregulated and 311 were downregulated). In the protein-protein interaction network, four hub modules and 30 hub genes were identified. To explore potential associations between gene and DN clinical features and to identify hub genes, the top 25% of genes with the greatest variance in the gene expression profiles were extracted for weighted correlation network analysis (WGCNA). There were ten genes (RNASE6, CD1C, SASH3, COL1A2, MS4A6A, CD163, CLEC10A, MOXD1, IQGAP2, GHR) identified as significant DN‐associated genes. Furthermore, the expression level of these hub genes was confirmed in the GSE96804 dataset. ConclusionsThese findings provide new insight into DN pathogenesis, which may enhance our fundamental knowledge of the molecular mechanisms underlying this disease.

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Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy

Cited by 19 publications

References 42 publications

Association of Genetic Polymorphisms in MicroRNAs With Type 2 Diabetes Mellitus in a Chinese Population

Association of Genetic Polymorphisms in MicroRNAs With Type 2 Diabetes Mellitus in a Chinese Population

WT1 and ACE mRNAs of blood extracellular vesicle as biomarkers of diabetic nephropathy

Identification of Hub Genes in Diabetic Nephropathy by an Integrated Bioinformatic Analysis

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