Urinary Extrecellular Vesicles miRNA Expression in Patients with Gitelman Syndrome: The Role of Hsa-let-7d-3p
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE282363 | GEO | 2025/12/03
REPOSITORIES: GEO
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Project description:Background High sodium intake is associated with arterial hypertension and cardiovascular disease, through mechanisms that go beyond hemodynamic changes, including endothelial dysfunction, oxidative stress, and induction of a pro-inflammatory milieu. The aim of this study was to assess the role of dietary sodium modulation on renal pathophysiology through evaluation of small RNA cargos on urinary extracellular vesicles (uEVs). Methods Fourteen high-risk normotensive subjects with normal kidney function were prospectively enrolled to undergo a low sodium diet (LSD) followed by high sodium diet (HSD). The uEVs were isolated from a 24h urine collection at the end of each diet phase and profiled by small RNA sequencing. Selected differentially expressed microRNAs (miRNAs) were validated in human proximal tubular cell line (HK-2 cells) to assess miRNA-mRNA target interactions. Results We identified 111 small RNA species of which 30 were significantly different between LSD and HSD. Bioinformatic network analysis showed that pathways related to the innate and adaptive immune system, interleukin and interferon signalling were enriched in HSD, whereas pathways related to peroxisome proliferator-activated receptor alpha (PPARα) regulation were enriched in LSD. In HK-2 cells, the inhibition of miR-320b, down-regulated in HSD, increased intercellular adhesion molecule 1 (ICAM-1), with renal pro-inflammatory effects. The inhibition of miR-10b-5p, down-regulated in LSD, increased PPARα, which has an anti-fibrotic and anti-inflammatory role in the kidney. Conclusions Small RNA characterization from uEVs revealed that HSD is associated with pro-inflammatory changes, potentially contributing to sodium-induced low-grade renal inflammation.
2025-12-12 | GSE288935 | GEO
Project description:Urinary extracellular vesicles (uEVs) are a promising source for biomarker discovery, including miRNAs. The optimal isolation method of uEVs for miRNA profiling in patients with proteinuria is unknown. Six different methods were compared for the isolation of microvesicles and these were compared to raw urine (method A). 2 methods failed and further analysis was performed with the following methods: ExoRNeasy (method C), modified protocol for ExoRNeasy (method E) and ultracentrifugation (method F). Different miRNAs are enriched by method C and F. No differences were observed between method C and E.
2020-08-01 | GSE102627 | GEO
Project description:Claudin-16 deficiency leads to renal salt wasting in humans and mice. Analysis of renal gene expression in Claudin-16 deficient mice, compared to heterozygous and wild type littermates, was performed to gain insights into molecular mechanisms compensating salt loss. Our results indicate the upregulation of known and putative genes for renal transcellular transporters. Furthermore, we could identify a transcript so far not associated with renal salt metabolism, which will provide a first link to a human electrolyte disorder disease.
2010-02-15 | GSE19961 | GEO
Project description:Novel therapies in autosomal dominant polycystic kidney disease (ADPKD) signal the need for markers of disease progression or response to therapy. This study aimed to identify disease-associated proteins in urinary extracellular vesicles (uEVs), which include exosomes, in patients with ADPKD. We performed quantitative proteomics on uEVs using a labeled approach (healthy vs. ADPKD) and then using a label-free approach in different subjects (healthy vs. ADPKD vs. non-ADPKD chronic kidney disease [CKD]). In both experiments, thirty proteins were consistently more abundant (≥ 2-fold) in ADPKD-uEVs compared with healthy and CKD uEVs. Of these proteins, periplakin, envoplakin, villin-1, complement C3 and C9 were selected for confirmation, because (1) they were also significantly overrepresented in pathway analysis, and (2) they have been previously implicated in the pathogenesis of ADPKD. Immunoblotting was used to validate the proteomics results, confirming higher abundances of the selected proteins in ADPKD-uEVs in three independent groups of ADPKD-patients. While villin-1, periplakin and envoplakin were more abundant in advanced stages of the disease, complement was already higher in uEVs of young ADPKD patients with preserved renal function. Furthermore, all five proteins correlated positively with height adjusted total kidney volume. The proteins of interest were also analyzed in kidney tissues from kidney-specific-tamoxifen-inducible Pkd1-deletion mice, demonstrating higher expression in more severe stages of the disease. In summary, proteomic analysis of uEVs identified plakins and complement as disease-associated proteins in ADPKD. These proteins are new candidates for evaluation as biomarkers or targets for therapy in ADPKD.
2016-03-15 | PXD003298 | Pride
Project description:Bladder cancer exhibits molecular heterogeneity that complicates early diagnosis and prognosis, and drives confounding clinical outcomes. Non–muscle invasive and muscle-invasive subtypes, especially for intermediate to high grade, carry a 25 – 50% progression-free survival rate, underscoring the need for high precision prognostic strategy. Urinary extracellular vesicles (uEVs) are promising carriers of tumor-derived RNAs and proteins. However, significant challenges in studying uEVs arise from the diverse cellular origin of uEVs associated with the dynamic composition of urine, which presents roadblocks for developing the clinical utility of uEVs. We introduced an AI-driven EV liquid biopsy pipeline that integrates (1) standardized EV isolation via NanoPom magnetic beads, (2) transcriptomic profiling for molecular subtyping, and (3) prognostic scoring algorithm. In a discovery cohort of 16 bladder cancer patients including both MIBC and NMIBC, we compared NanoPom isolated uEVs with ExoEasy and Fujifilm MagCapture isolated uEVs, for identifying bladder cancer subtype-specific gene signatures, and externally validated them using UCSC Xena. The result outperformed currently reported bladder cancer diagnostic biomarkers from assays including Galeas, CxBladder, and Xpert. In a validation cohort of matched 7 patient plasma samples, we confirmed with plasma derived EVs for correlating with urinary EV biomarkers from NGS sequencing. The prognostic score stratified patients into low-, intermediate-, and high-grade risk groups based on Xena's bladder cancer survival outcomes. Our AI-driven uEV liquid biopsy pipeline proves the concept for high precision bladder cancer subtyping and prognosis, which could potentially facilitate treatment decision and lead to advanced profiling of bladder tumor biology using uEV liquid biopsy.
2025-09-28 | GSE308996 | GEO
Project description:Novel therapies in autosomal dominant polycystic kidney disease (ADPKD) signal the need for markers of disease progression or response to therapy. This study aimed to identify disease-associated proteins in urinary extracellular vesicles (uEVs), which include exosomes, in patients with ADPKD. We performed quantitative proteomics on uEVs using a labeled approach (healthy vs. ADPKD) and then using a label-free approach in different subjects (healthy vs. ADPKD vs. non-ADPKD chronic kidney disease [CKD]). In both experiments, thirty proteins were consistently more abundant (? 2-fold) in ADPKD-uEVs compared with healthy and CKD uEVs. Of these proteins, periplakin, envoplakin, villin-1, complement C3 and C9 were selected for confirmation, because (1) they were also significantly overrepresented in pathway analysis, and (2) they have been previously implicated in the pathogenesis of ADPKD. Immunoblotting was used to validate the proteomics results, confirming higher abundances of the selected proteins in ADPKD-uEVs in three independent groups of ADPKD-patients. While villin-1, periplakin and envoplakin were more abundant in advanced stages of the disease, complement was already higher in uEVs of young ADPKD patients with preserved renal function. Furthermore, all five proteins correlated positively with height adjusted total kidney volume. The proteins of interest were also analyzed in kidney tissues from kidney-specific-tamoxifen-inducible Pkd1-deletion mice, demonstrating higher expression in more severe stages of the disease. In summary, proteomic analysis of uEVs identified plakins and complement as disease-associated proteins in ADPKD. These proteins are new candidates for evaluation as biomarkers or targets for therapy in ADPKD.
2016-10-21 | MSV000080264 | MassIVE
Project description:Autosomal dominant tubulointerstitial kidney disease-subtype hepatocyte nuclear factor 1β (ADTKD-HNF1β) is caused by pathogenic variants in or deletions of the gene encoding transcription factor HNF1β. Patients with the same mutation have variable renal and extrarenal phenotypes, including renal cysts, diabetes, and electrolyte disturbances. The aim of this exploratory study was to provide insight whether pathophysiological effects in the kidney of ADTKD-HNF1β patients are visible by analysing their urinary extracellular vesicle (uEV) proteome. We isolated uEVs collected from patients with ADTKD-HNF1β and included patients with ADPKD and patients with CKD as controls. Subsequently, LC-MS/MS proteomics, and differential and pathway enrichment analyses were performed. Transcriptional targets of HNF1β were selected with ChIP-sequencing to study changes in protein abundance due to loss of HNF1β, and correlation analyses with clinical features were performed. We found differential enrichment of ciliary proteins IFT57, IFT74, IFT81 and IFT88 (adjusted p-value < 0.1), significant enrichment of pathways involved in cell-cell adhesion, and the depletion of several Serpins in patients with ADTKD-HNF1β and APDKD, compared to patients with CKD. We identified differential enrichment of nine HNF1β transcriptional targets between patients with ADTKD-HNF1β and patients with CKD, and we demonstrated that Serpin abundance negatively correlated with eGFR in patients with ADTKD-HNF1β (R = -0.52). The uEV proteome of patients with ADTKD-HNF1β shows a significant enrichment in proteins involved in renal cysts development, with resemblance to ADPKD. These changes provide new insight in the pathophysiology of ADTKD-HNF1β. Their onset and association with cyst development and kidney function decline warrants further study.
2025-03-06 | PXD050720 | Pride
Project description:Hermansky-Pudlak syndrome type 1 (HPS-1) is a rare, autosomal recessive disorder caused by defects in the biogenesis of lysosome-related organelles complex-3 (BLOC-3). Impaired kidney function is among its clinical manifestations. To investigate HPS-1 renal involvement, we employed 1D-gel-LC–MS/MS and compared the protein composition of urinary extracellular vesicles (uEVs) from HPS-1 patients to normal control individuals. We identified 1029 proteins, 149 of which were altered in HPS-1 uEVs. Ingenuity Pathway Analysis revealed disruptions in mitochondrial function and the LXR/RXR pathway that regulates lipid metabolism, which is supported by our novel Hps1 knockout mouse. Serum concentration of the LXR/RXR pathway protein ApoA1 in our patient cohort was positively correlated with kidney function (with the estimated glomerular filtration rate or eGFR). uEVs can be used to study epithelial cell protein trafficking in HPS-1 and may provide outcome measures for HPS-1 therapeutic interventions.
2025-07-07 | PXD063765 | Pride
Project description:Enrolled 24 participants, including twelve renal biopsy-proven T2DN and twelve T2DM, and isolated uEV s by ultracentrifugation to perform adequate parallel microarrays for mRNAs, lncRNAs and circRNAs and sequencing for miRNAs.One hundred mL of first-morning urine was collected.All urine samples were retained and immediately transferred to the laboratory and centrifuged at 2500 x g at 4°C for 15 min using a horizontal rotor (Dynamica V14R Pro, UK) and at 17,000 x g at 4°C for 40 min using a fixed angle rotor (FA15C rotor, Dynamica, UK). Supernatants were filtered using 0.22µm PES filters (Jet Bio-Filtration, Guangzhou, China) and transferred to new centrifuge tubes and stored at -80 degrees. After overnight melting through a 4 degree, ultracentrifuged at 200,000 xg at 4°C for 2h in a fixed angle P45AT rotor (k factor= 130, CP100NX, Hitachi, Tokyo, Japan) and repeat again after resuspending the pellet in PBS. Supernatants were discarded and the pellets were washed in PBS to obtain the uEVs.
2023-11-27 | GSE218929 | GEO
Project description:Urinary Extrecellular Vesicles miRNA Expression in Patients with Gitelman Syndrome: The Role of Hsa-let-7d-3p
| PRJNA1188204 | ENA