Biomarker Potential of Urine miR-451 at Different Stages of Diabetic Nephropathy

Sayilar, Emel İşiktaş

doi:10.4172/2155-6156.1000650

Cited by 11 publications

(13 citation statements)

References 34 publications

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“…As opposed to our observation, Sayilar and colleagues (Sayilar et al, 2016) have found significantly low urinary, but higher plasma, miR-451 in CKD patients (stages 3 and 5) as compared to healthy volunteers. The reason for this discrepancy could be the stage of renal disease at which the subjects were analyzed; our subjects were in the early-stage of CKD (1 or 2).…”

Section: Discussioncontrasting

confidence: 99%

miR-451 Loaded Exosomes Are Released by the Renal Cells in Response to Injury and Associated With Reduced Kidney Function in Human

et al. 2020

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Micro-RNAs (miRs) encapsulated inside urinary exosomes (uEs) have the potential as early biomarkers. Previously, we reported that a rise in uE miR-451 predicted albuminuria in diabetic rats; however, whether the rise was protective or detrimental, and occurred in response to injury or general hyperglycemia, was unknown. To address this, we studied both human and rat models of renal disease. In humans, uE miR-451 was approximately twofold higher in subjects with early-stage chronic kidney disease (CKD; serum creatinine < 2.0 mg/dl; n = 28), as compared to age-matched healthy controls (n = 23), and had a significant negative correlation with estimated glomerular filtration rate (eGFR) (r 2 = −0.10, p = 0.01). Subgroup analysis of CKD subjects showed that those without diabetes had slightly (∼30%) but significantly higher uE miR-451 as compared to those with diabetes, with no differences in albumin excretion, eGFR, serum sodium, and potassium. Using human proximal tubule (hPT) cells, we found that locked nucleic acid (LNA) inhibition of miR-451 resulted in a significant increase in the messenger RNA (mRNA) expression of kidney-injury-associated miR-451 targets, e.g., CAB39, TBX1, and YWHAZ, as compared to treatment with a control LNA. Moreover, hPT cells and their secreted exosomes showed an increase in miR-451 in response to mechanical injury but not high glucose (20 versus 5 mM). For further proof of concept, in diabetic rats, we showed that atorvastatin (AT), a treatment proven to attenuate renal injury without affecting systemic glucose levels, reduced uE miR-451 with the concomitant restoration of renal miR-451. These data elucidate the stimuli for renal miR-451 expression and exosomal release and support its role as a therapeutic target and early biomarker for renal injury in humans.

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Section: Discussioncontrasting

confidence: 99%

miR-451 Loaded Exosomes Are Released by the Renal Cells in Response to Injury and Associated With Reduced Kidney Function in Human

et al. 2020

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“…In the present study, plasma microRNA-451 showed a significant increase in patients with DM and mild to moderate end-stage renal disease either with or without albuminuria. These findings were similar to the previous experimental study by Zhang et al [ 27 , 28 ].…”

Section: Discussionsupporting

confidence: 93%

“…There was a significant positive correlation between the urinary microRNA-451 level and the eGFR value in association with a negative correlation between the plasma microRNA-451 level and eGFR, which supports the role of microRNA-451 as a predictor of disease progression and the development of renal fibrosis [ 30 ]. Previous studies for microRNA-451 revealed an early increase in its level in the tissue of the kidney and later on a decrease in urine, reflecting the increased activity of signal pathways such as MAPK9 and SMAD3 in association with the process of nephropathy development [ 27 , 30 ]. Therefore, the expression of microRNA-451 in urine might reflect the glomerular filtration rate and renal production of this microRNA.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-451 as an Early Predictor of Chronic Kidney Disease in Diabetic Nephropathy

Abdelsalam

Wahab

Zaki

et al. 2020

International Journal of Nephrology

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Background. Diabetes mellitus is the leading cause of end-stage renal disease worldwide. Microalbuminuria is the cornerstone for the diagnosis of diabetic nephropathy. However, it is an inadequate marker for early diagnosis. MicroRNAs are not only new and promising markers for early diagnosis but also, but they may also play a role in the prevention of disease progression. Methods. This study included ninety patients with type 2 DM in addition to 30 control subjects. MicroRNA-451 expression in blood and plasma using real-time PCR was evaluated in addition to the classic diabetic nephropathy markers (serum creatinine, urinary albumin, and eGFR). Results. There was a significant difference between the studied groups versus control regarding serum creatinine, eGFR, urinary, and plasma microRNA-451 with p=0.0001. Patients with eGFR 60 ml/min/1.73 m2 showed a significantly higher plasma microRNA-451 (29.6 ± 1.6) and significantly lower urinary microRNA-451 (21 ± 0.9) in comparison to patients with eGFR >60 ml/min/1.73 m2 and p=0.0001. eGFR showed a positive correlation with urinary microRNA-451 and negative correlation with both plasma microRNA-451 and urinary albumin. Both plasma and urinary microRNA-451 are highly sensitive and specific markers for chronicity in diabetic nephropathy patients with sensitivity of 90.9% and 95.5% and specificity of 67.6% and 95.6%, respectively. Conclusion. MicroRNA-451 is a promising early biomarker for chronic kidney disease in diabetic nephropathy with high sensitivity and specificity.

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“…This reduction of miR-192 expression removed the suppression of the E box repressors, Zeb1, and Zeb2 expressions, which are the inducers of the TGFB pathway, and further promoted TGFB-induced downstream activation of other miRNAs to promote renal hypertrophy and ECM accumulation (Kato et al, 2007). One example of the TGFBdownstream miRNAs is the miR-21, which is the most wellknown miRNA in DN and its expression was upregulated in both human DN and mice models (Zhang et al, 2009;Sayilar et al, 2016;Chen et al, 2018;Wang et al, 2019a). MiR-21 negatively regulates the expression of Phosphatase and tensin homolog (PTEN) and matrix metalloproteinases (Chau et al, 2012).…”

Section: Micrornas In Renal Hypertrophy and Ecm Accumulationmentioning

confidence: 99%

“…MiR-21 negatively regulates the expression of Phosphatase and tensin homolog (PTEN) and matrix metalloproteinases (Chau et al, 2012). Hyperglycemia condition upregulates miR-21 expression in the plasma and urine samples (Sayilar et al, 2016). In a study of DN patients, miR-21 expression was elevated in the kidney biopsy and correlated with the podocyte cell damage, together with a reduced metalloproteinase inhibitor-3 (TIMP3) expression (Chen et al, 2018).…”

Section: Micrornas In Renal Hypertrophy and Ecm Accumulationmentioning

confidence: 99%

Interactions Among Non-Coding RNAs in Diabetic Nephropathy

et al. 2020

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Diabetic Nephropathy (DN) is the most common cause of End-stage renal disease (ESRD). Although various treatments and diagnosis applications are available, DN remains a clinical and economic burden. Recent findings showed that noncoding RNAs (ncRNAs) play an important role in DN progression, potentially can be used as biomarkers and therapeutic targets. NcRNAs refers to the RNA species that do not encode for any protein, and the most known ncRNAs are the microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Dysregulation of these ncRNAs was reported before in DN patients and animal models of DN. Importantly, there are some interactions between these ncRNAs to regulate the crucial steps in DN progression. Here, we aimed to discuss the reported ncRNAs in DN and their interactions with critical genes in DN progression. Elucidating these ncRNAs regulatory network will allow for a better understanding of the molecular mechanisms in DN and how they can act as new biomarkers for DN and also as the potential targets for treatment.

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Biomarker Potential of Urine miR-451 at Different Stages of Diabetic Nephropathy

Cited by 11 publications

References 34 publications

miR-451 Loaded Exosomes Are Released by the Renal Cells in Response to Injury and Associated With Reduced Kidney Function in Human

miR-451 Loaded Exosomes Are Released by the Renal Cells in Response to Injury and Associated With Reduced Kidney Function in Human

MicroRNA-451 as an Early Predictor of Chronic Kidney Disease in Diabetic Nephropathy

Interactions Among Non-Coding RNAs in Diabetic Nephropathy

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