MicroRNAs as Biomarkers for Nephrotic Syndrome

Tsuji, Kenji; Kitamura, Shinji; Wada, Jun

doi:10.3390/ijms22010088

Cited by 22 publications

(23 citation statements)

References 79 publications

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“…In a urinary sample, sediment cells, proteins, miRNAs, and mRNAs can be used as biomarkers to diagnose kidney injury (22)(23)(24). The number of cells in urinary sediment samples is small, and the level of total RNA is too low to be used for RNAseq assay.…”

Section: Discussionmentioning

confidence: 99%

Urinary Sediment mRNA Level of CREBBP and CYBA in Children With Steroid-Resistant Nephrotic Syndrome

Shou

Xiang

et al. 2022

Front. Immunol.

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BackgroundThis study aimed to evaluate gene expression patterns in urinary sediment samples of children with steroid-resistant nephrotic syndrome (SRNS).MethodsThe messenger RNA (mRNA) levels of 770 immune-related genes were detected using a NanoString nCounter platform. To verify the NanoString results, quantitative analysis of nine gene mRNAs was performed using real-time RT-PCR in more samples.ResultsFirstly, compared with the steroid-sensitive nephrotic syndrome (SSNS) group (n=3), significant changes were observed in the mRNA level of 70 genes, including MAP3K14, CYBA, SLC3A2, CREB-binding protein (CREBBP), CD68, forkhead box P1 (FOXP1), CD74, ITGB2, IFI30, and so forth, in the SRNS group (n=3). A total of 129 children with idiopathic nephrotic syndrome (INS), 15 with acute glomerulonephritis, and 6 with immunoglobulin A nephropathy (IgAN) were enrolled to verify the NanoString results. Compared with patients with IgAN, those with INS had significantly lower levels of FOXP1 (P=0.047) and higher levels of CREBBP (P=0.023). Among SSNS, the mRNA level of ITGB2 was significantly lower in the non-relapse group than in the non-frequent relapse and frequent-relapse groups (P=0.006). Compared with the SSNS group, CREBBP was significantly elevated in the SRNS group (P=0.02). Further, CYBA significantly decreased in the SRNS group (P=0.01). The area under the curve (AUC) for CREBBP and CYBA was 0.655 and 0.669, respectively. CREBBP had a sensitivity of 83.3% and a specificity of 49.4% and CYBA had a sensitivity of 58.3% and a specificity of 83.1% to rule out SSNS and SRNS. The diagnosis value was better for CREBBP+CYBA than for CREBBP or CYBA alone, indicating that the combination of CREBBP and CYBA was a more effective biomarker in predicting steroid resistance (AUC=0.666; sensitivity=63.9%; specificity=76.4%).ConclusionsThis study was novel in investigating the urinary sediment mRNA level in children with INS using high-throughput NanoString nCounter technology, and 70 genes that may relate to SRNS were found. The results revealed that the urinary sediment mRNA level of ITGB2 was significantly lower in the non-relapse group than in the non-frequent relapse and frequent-relapse groups. Meanwhile, CREBBP was significantly elevated and CYBA was significantly lowered in the SRNS group compared with the SSNS group.

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Section: Discussionmentioning

confidence: 99%

Urinary Sediment mRNA Level of CREBBP and CYBA in Children With Steroid-Resistant Nephrotic Syndrome

Shou

Xiang

et al. 2022

Front. Immunol.

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“…Urine is an ideal source of biomarkers and provide valuable insight on renal pathophysiology. Podocyte cytoskeleton is regulated by several miRNAs, including miR-30, miR-132, miR-134 and miR-29a (Tsuji et al, 2020) [27]. In the present study, the observed upregulation of all the four miRNAs (miR-1, mir-215, miR-335, let-7a) in both SSNS and SRNS versus healthy controls implies of podocyte injury, aberrant expression of these microRNAs and their consequent role in the pathogenesis of NS.…”

Section: Discussionmentioning

confidence: 99%

Urinary MicroRNA Expression Analysis of miR-1, miR-215, miR-335, Let-7ain Childhood Nephrotic Syndrome

Priya

Venkatesan

Charmine

et al. 2021

Preprint

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Background Recently, urinary exosomal miRNAs are gaining increasing attention as their expression profiles are often associated with specific diseases and they exhibit great potential as noninvasive biomarkers for the diagnosis of various diseases. The present study was aimed to evaluate the expression status of selected miRNAs (miR-1, miR-215-5p, miR-335-5p and let-7a-5p) in urine samples from children with NS [steroid sensitive (SSNS)] and [steroid resistant (SRNS)] along with healthy control group.Methods MicroRNA isolation was carried out in urine samples collected from SSNS (100 nos), SRNS (100 nos), and healthy controls (50 nos) using MiRNeasy Mini Kit, followed by cDNA conversion for all the four selected miRNAs using Taqman advanced miRNA cDNA synthesis kit and their expression was quantified by Taqman Advanced miRNA assay kits using Real Time PCR Machine and Rotogen-Q in SSNS and SRNS patients and healthy control subjects.ResultsQuantification of all the four miRNAs (miR-1, mir-215, miR-335, let 7a) were found to be upregulated in both SSNS and SRNS as compared to control group. Further, the comparison of microRNAs within the case groups revealed significant downregulation of three microRNAs - miR-1, miR-215, miR- 335 and upregulation of let-7a in SRNS group as compared to SSNS. The t-test performed for all the four miRNAs was found to be statistically significant. ConclusionsThe aberrant expression of all the four microRNAs in both SSNS and SRNS as compared to healthy subjects may serve as novel biomarkers to distinguish between NS and healthy controls. The differential expression of microRNA let-7a is useful to discriminate SSNS and SRNS.

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“…(Patnaik et al, 2018). The miRNA‐30a remains a plausible molecular marker to predict drug resistance and pathological type of NS (Sui et al, 2014). Intrarenal expression of miR‐19b was overexpressed (2.5–3 fold) in MesPGN renal tissues.…”

Section: Mirnas In Fsgsmentioning

confidence: 99%

“…miRNAs in peripheral blood might be treated as the molecular biomarkers of human disease. Sui et al (2014) studied the expression levels of three microRNAs (miR‐181a, miR‐483‐5p, and miR‐557) in the serum of NS patients and found miR‐181a alone was significantly upregulated in patients with NS as compared with healthy controls. Zhang et al (2015) profiled miRNAs in plasma samples from a cohort of patients with FSGS and found that miR‐186 expression was correlated with proteinuria level and might be served as biomarkers for FSGS (Zhang et al, 2015).…”

Section: Circulating and Urinary Mirnasmentioning

confidence: 99%

MicroRNAs in childhood nephrotic syndrome

Dhandapani

Venkatesan

Charmine

2021

Journal Cellular Physiology

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The discovery of microRNAs (miRNAs) has opened up new avenues of research to understand the molecular basis of a number of diseases. Because of their conservative feature in evolution and important role in the physiological function, microRNAs could be treated as predictors for disease classification and clinical process based on the specific expression. The identification of novel miRNAs and their target genes can be considered as potential targets for novel drugs. Furthermore, currently, the circulatory and urinary exosomal miRNAs are gaining increasing attention as their expression profiles are often associated with specific diseases, and they exhibit great potential as noninvasive or minimally invasive biomarkers for the diagnosis of various diseases. The remarkable stability of these extracellular miRNAs circulating in the blood or excreted in the urine underscored their key importance as biomarkers of certain diseases. There is voluminous literature concerning the role of microRNAs in other diseases, such as cardiovascular diseases, diabetic nephropathy, and so forth. However, little is known about their diagnostic ability for the pediatric nephrotic syndrome (NS). The present review article highlights the recent advances in the role of miRNAs in the pathogenesis and molecular basis of NS with an aim to bring new insights into further research applications for the development of new therapeutic agents for NS.

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MicroRNAs as Biomarkers for Nephrotic Syndrome

Cited by 22 publications

References 79 publications

Urinary Sediment mRNA Level of CREBBP and CYBA in Children With Steroid-Resistant Nephrotic Syndrome

Urinary Sediment mRNA Level of CREBBP and CYBA in Children With Steroid-Resistant Nephrotic Syndrome

Urinary MicroRNA Expression Analysis of miR-1, miR-215, miR-335, Let-7ain Childhood Nephrotic Syndrome

MicroRNAs in childhood nephrotic syndrome

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