Dataset Information

Human Urinary Proteome in Vesicoureteral Reflux

ABSTRACT: Vesicoureteral reflux (VUR) is a common pediatric condition that predisposes children to renal damage after urinary tract infection (UTI). We profiled the urinary proteome of VUR patients with recurrent UTI and renal scarring to identify potential biomarkers characterizing this condition. Urine was obtained from 22 age-matched controls and 22 patients with low grade VUR (1-3 out of 5), renal scarring, and history of recurrent UTI. Proteins extracted from these samples were analyzed by mass spectrometry for protein identification and quantitation for comparison.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Urine

SUBMITTER: Patricia Cho

LAB HEAD: Richard S. Lee

PROVIDER: PXD010469 | Pride | 2018-10-05

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 103

Publications

Characterizing Patients with Recurrent Urinary Tract Infections in Vesicoureteral Reflux: A Pilot Study of the Urinary Proteome.

Vitko Dijana D Cho Patricia S PS Kostel Stephen A SA DiMartino Shannon E SE Cabour Lily D LD Migliozzi Matthew A MA Logvinenko Tanya T Warren Peter G PG Froehlich John W JW Lee Richard S RS

Molecular & cellular proteomics : MCP 20200102 3

Recurrent urinary tract infections (UTIs) pose a significant burden on the health care system. Underlying mechanisms predisposing children to UTIs and associated changes in the urinary proteome are not well understood. We aimed to investigate the urinary proteome of a subset of children who have vesicoureteral reflux (VUR) and recurrent UTIs because of their risk of developing infection-related renal damage. Improving diagnostic modalities to identify UTI risk factors would significantly alter t ...[more]

PMID: 31896675

Similar Datasets

Project description:Renal scarring is a serious complication of chronic pyelonephritis due to vesicoureteral reflux, and requires specific biomarker for indication of early intervention. We investigated global expression profile of kidney during renal scarring formation using rat pyelonephritis model. An inoculum of the DS-17 strain Escherchia coli was injected directly into renal cortex of Wister rat. Histologically, renal scarring developed during 3 and 4 weeks after injection. The time course expression profile of approximately 20,500 genes was analyzed using high density oligonucleotide microarray followed by validation using real time RT-PCR. Most of up-regulated genes during this experimental renal scarring were associated with immune and defense response, including cytokines, chemokines, their receptors, complements, and adhesion molecules as well as proteins related to extra cellular matrix. These genes were up-regulated as early as 1 week after injection when histological examination did not show fibrotic change yet, peaked at 2 weeks and gradually decreased thereafter. However, a subset of cytokine genes is persistently activated even in 6 weeks after the injection, which are involved in TGF-Î² related tissue regeneration pathway or IL-1Î² related pathway. The products of these genes may potentially be the source of novel non-invasive diagnostic or prognostic biomarkers for renal scarring. Experiment Overall Design: Experimental pyelonephritis was produced by standard method of direct infection of rat kidney. In brief, animals were anesthetized with pentobarbital intraperitoneally. The kidneys were exposed through a midline abdominal incision. An inoculum of 1x109 colony-forming units / 0.1 ml of Escherchia coli was injected directly into bilateral renal cortex of Wister rat using 26-gauge needle. We used DS-17 or NU-14 strains, both of which has type 1 and P pili, and SEC strain, which has only type 1 pili. Control rats received isotonic saline instead of bacterial solution. Both test and control kidneys were harvested at 1, 2, 4 and 6 weeks after injection. The kidney samples (1x1x2 mm each) were obtained including the injection site, which was easily identified by surface color change. Then we cut the kidney into half; one was used for microscopic examination and the other half was immediately frozen in liquid nitrogen for later RNA extraction.

Project description:Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are severe inflammatory disorders that often lead to rapid and irreversible organ failure. Rapid progressive glomerulonephritis (RPGN) is a particularly frequent renal manifestation and often leads to extensive glomerular scarring and interstitial fibrosis, resulting in chronic kidney disease and end stage renal failure. Current management options of AAV and its sequelae are limited and common therapies have serious side effects that impair quality of life. A better understanding of the deleterious scarring process of AAV may help to identify novel mechanisms and potential targets for therapy. However, robust murine models of scarring RPGN are still lacking. Here, we present a novel murine model of severe RPGN that recapitulates both acute injury and the subsequent glomerular and interstitial scarring that is based on combined administration of antibodies against the glomerular basement membrane (GBM) and myeloperoxidase (MPO), and bacterial lipopolysaccharides (LPS). Renal injury presented with severe hematuria, glomerular necrosis and crescent formation at 12 days, and consequent glomerular scarring 29 days after initial treatment. We observed increased expression of matrisomal components such as collagens, fibronectin, tenascin-C, in accordance with human AAV as deduced from analysis of gene expression microarray data and tissue staining. Moreover, we observed tissue infiltration by neutrophils, macrophages, T cells and myofibroblasts upon injury. Inhibition of CXCR4 using AMD3100 led to histological and molecular changes in injury with reduced chemokine expression and lower immune cells activation. Using mass-spectrometric proteome analysis, we provide a comprehensive overview of molecular and cellular changes in our AAV model. Altogether, we demonstrate a novel RPGN model that enables the study of matrisomal changes both in disease and upon intervention, as exemplified via CXCR4 inhibition, which could prove to be a viable pharmacological tool and provide matrix as novel targeting opportunity.

			Action	DRS
	150828_PC_VUR_C1077.msf	Msf
	150828_PC_VUR_C1077.raw	Raw
	150828_PC_VUR_C1093.msf	Msf
	150828_PC_VUR_C1093.raw	Raw
	150828_PC_VUR_C1133.msf	Msf