Dataset Information

Differential Expression of Urinary Exosomal Small RNAs in Idiopathic Membranous Nephropathy.

ABSTRACT:

Background

Idiopathic membranous nephropathy (IMN) is a major cause of adult nephrotic syndromes, and reliable noninvasive biomarkers for diagnosis and monitoring are urgently needed. In this study, we performed small RNA (sRNA) sequencing to explore sRNA profiles of urinary exosomes derived from IMN patients and healthy controls (CON) to provide clues for identifying novel noninvasive sRNA biomarkers for IMN.

Methods

Urine samples were collected from five healthy controls and six patients with IMN. High-throughput sequencing was used to screen sRNA expression profiles of urinary exosomes from patients with IMN in two independent cohorts.

Results

Urinary exosomes were successfully isolated and used to obtain exosomal sRNAs. We screened 131 differentially expressed miRNAs, including 28 specifically expressed miRNAs, then explored the top 10 specifically expressed miRNAs in all IMN individuals. The specifically expressed miRNAs and differentially expressed miRNAs provide potential biomarkers for IMN. Additionally, we discovered numerous sRNAs derived from genomic repetitive sequences, which could represent an exciting new area of research.

Conclusion

Herein, we revealed significant differences in expression profiles of urinary exosomal miRNAs and repetitive region-derived sRNAs between patients with IMN and healthy controls. The findings could facilitate the development of potential molecular targets for membranous nephropathy.

SUBMITTER: Zhang J

PROVIDER: S-EPMC7785370 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Differential Expression of Urinary Exosomal Small RNAs in Idiopathic Membranous Nephropathy.

Zhang Jinshi J Zhu Yifan Y Cai Ruyi R Jin Juan J He Qiang Q

BioMed research international 20201229

<h4>Background</h4>Idiopathic membranous nephropathy (IMN) is a major cause of adult nephrotic syndromes, and reliable noninvasive biomarkers for diagnosis and monitoring are urgently needed. In this study, we performed small RNA (sRNA) sequencing to explore sRNA profiles of urinary exosomes derived from IMN patients and healthy controls (CON) to provide clues for identifying novel noninvasive sRNA biomarkers for IMN.<h4>Methods</h4>Urine samples were collected from five healthy controls and six ...[more]

PMID: 33457405

Similar Datasets

Project description:Background: IgA nephropathy (IgAN) is one of the most common forms of primary glomerulonephritis. Recent studies have indicated that small noncoding RNAs, such as tRNA-derived small RNAs (tsRNAs), might be novel biomarkers for glomerulonephritis. We therefore investigated the potential roles and possible functions of the tsRNAs in IgAN.Method: Peripheral blood mononuclear cells (PBMCs) were extracted from blood samples of the patients with IgAN and healthy control groups. The expression profiles of tsRNAs were assessed by small RNA sequencing (RNA-Seq) in PBMCs of the IgAN and control groups. Dysregulated tsRNAs were selected for validation by quantitative real-time polymerase chain reaction (qRT-PCR). Target gene prediction and enrichment were performed by bioinformatics analysis.Results: The results revealed that 143 significantly upregulated and 202 significantly downregulated tsRNAs were differentially altered in the IgAN group compared with the control group. Five upregulated tsRNAs (tRF-Val-AAC-007, tRF-Ala-AGC-063, tRF-Gln-CTG-010, tRF-Tyr-GTA-011 and tRF-Thr-AGT-007) and 3 downregulated tsRNAs (tiRNA-Val-TAC-004, tRF-Gly-CCC-005 and tRF-His-GTG-006) were selected for validation by qRT-PCR; the results were consistent with the sequencing data. Gene Ontology (GO) analysis revealed that the target genes predicted by upregulated tsRNAs were mostly enriched in "nucleic acid metabolic process,' "intracellular part,' and "ion binding,' whereas the target genes predicted by downregulated tsRNAs were mostly enriched in "regulation of cellular component organization,' "membrane-bound organelle,' and "ion binding.' Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes predicted by upregulated tsRNAs were mostly enriched in "herpes simplex virus 1 infection,' whereas the target genes predicted by downregulated tsRNAs were mostly enriched in "circadian rhythm CONCLUSIONS:: The present study confirmed the differential expression of tsRNAs in patients with IgAN, and these dysregulated tsRNAs might be novel potential targets for the diagnosis and treatment of IgAN.

Project description:Introduction: Minimal change disease (MCD) is a major cause of nephrotic syndrome. With a substantial number of patients requiring long-term immunosuppression leading to significant morbidity, the study aim was to determine MCD glomerular transcriptome to serve as a basis for biomarker discovery and novel drug target identification. Animal work showed podocyte injury induced by IL-7/IL-7R signaling (Zhai S, BBRC, 2018). Methods: Renal biopsies from adult patients representing the following groups were selected from the Norwegian Kidney Biopsy Registry: MCD (n=14), as well as normal tissue (n=8) and primary membranous nephropathy (MN; n=12) as the two reference groups. RNA for 75 base-pair paired-end RNASeq was obtained by dissecting glomeruli via laser capture microdissection (LCM) from FFPE cross-sections. Systematic delineation of condition-specific alteration in transcriptional landscapes was achieved by combining pathway-centered analyses with methodologies derived from network science and integrating multiple bioinformatics resources. Results: Compared to normal glomeruli, glomeuli from MCD displayed an inflammatory signature that appeared to be predominantly governed by the IL1 and IL7 systems. While enrichment of IL1 production and secretion was a shared feature of MCD and MN compared to normal tissue, responses involving IL7 pathway activation were unique to MCD. Indeed, IL7R expressed by glomeruli was the most up-regulated gene of to the interleukin-family in MCD vs normal controls. IL7 pathway activation was paralleled by significant enrichment in adaptive immune system processes and transcriptional regulation and depletion in pathways related to energy metabolism and transcription. Downregulation of these organ function-related themes again occurred predominately in MDC and were significantly less pronounced in MN. Conclusion: Our results demonstrate that archival FFPE-biopsies can be used to generate glomeruli-specific gene expression profiles suitable for systematic delineation of kidney-associated diseases. Here the latter provides a data-driven rationale to experimentally address these MCD-specific features as biomarkers and as novel drug targets. In this context inhibiting activation of the IL7 pathway may be particularly promising.

Dataset Information

Differential Expression of Urinary Exosomal Small RNAs in Idiopathic Membranous Nephropathy.

Background

Methods

Results

Conclusion

Publications

Differential Expression of Urinary Exosomal Small RNAs in Idiopathic Membranous Nephropathy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets