Evidence map›Paper›PMID 25793258›Full record

ArticlePLoS neglected tropical diseases2015

Proteomic analysis of urine exosomes reveals renal tubule response to leptospiral colonization in experimentally infected rats.

Satish P RamachandraRao, Michael A Matthias, Chanthel Kokoy-Mondragon, Chanthel-Kokoy Mondrogon, Eamon Aghania, Cathleen Park, Casey Kong, Michelle Ishaya, Assael Madrigal, Jennifer Horng and 9 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.3field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Pathology and pathogenesis of human leptospirosis: a commented review.Revista do Instituto de Medicina Tropical de Sao Paulo · 2018
    Review
  8. Review
  9. Extracellular Vesicles in Renal Pathophysiology.Frontiers in molecular biosciences · 2017
    Review
  10. Article
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 3 institutions in 2 countries.

Satish P RamachandraRaoUniversity of California, San Diego Department of Medicine, Division of Nephrology-Hypertension, San Diego, California, United States of America; University of California, San Diego Department of Pediatrics, Center for Promotion of Maternal Health and Infant Development, La Jolla, California, United States of America.
Michael A MatthiasUniversity of California, San Diego Department of Medicine, Division of Infectious Diseases, La Jolla, California, United States of America.
Chanthel Kokoy-Mondragon
Chanthel-Kokoy MondrogonUniversity of California, San Diego Department of Medicine, Division of Nephrology-Hypertension, San Diego, California, United States of America.
Eamon AghaniaUniversity of California, San Diego Department of Medicine, Division of Nephrology-Hypertension, San Diego, California, United States of America.
Cathleen ParkUniversity of California, San Diego Department of Medicine, Division of Nephrology-Hypertension, San Diego, California, United States of America.
Casey KongUniversity of California, San Diego Department of Medicine, Division of Nephrology-Hypertension, San Diego, California, United States of America.
Michelle IshayaUniversity of California, San Diego Department of Medicine, Division of Nephrology-Hypertension, San Diego, California, United States of America.
Assael MadrigalUniversity of California, San Diego Department of Medicine, Division of Nephrology-Hypertension, San Diego, California, United States of America.
Jennifer HorngUniversity of California, San Diego Department of Medicine, Division of Nephrology-Hypertension, San Diego, California, United States of America.
Roni KhoshabaUniversity of California, San Diego Department of Medicine, Division of Nephrology-Hypertension, San Diego, California, United States of America.
Anousone BounkhounUniversity of California, San Diego Department of Medicine, Division of Nephrology-Hypertension, San Diego, California, United States of America.
Fabrizio BasilicoProteomics and Metabolomics Laboratory (Istituto di Tecnologie Biomediche-Consiglio Nazionale delle Ricerche (ITB-CNR); Segrate (MI), Italy.
Antonella De PalmaProteomics and Metabolomics Laboratory (Istituto di Tecnologie Biomediche-Consiglio Nazionale delle Ricerche (ITB-CNR); Segrate (MI), Italy.
Anna Maria AgrestaProteomics and Metabolomics Laboratory (Istituto di Tecnologie Biomediche-Consiglio Nazionale delle Ricerche (ITB-CNR); Segrate (MI), Italy.
Linda AwdishuUniversity of California, San Diego Department of Medicine, Division of Nephrology-Hypertension, San Diego, California, United States of America.
Robert K NaviauxUniversity of California, San Diego Departments of Medicine, Pediatrics and Pathology, San Diego, California, United States of America.
Joseph M VinetzUniversity of California, San Diego Department of Medicine, Division of Infectious Diseases, La Jolla, California, United States of America.
Pierluigi MauriProteomics and Metabolomics Laboratory (Istituto di Tecnologie Biomediche-Consiglio Nazionale delle Ricerche (ITB-CNR); Segrate (MI), Italy; Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
University of California, San Diego · USIstituto per le Tecnologie Didattiche · ITInstitute of Biomedical Technologies · IT

Funding

UAB-UCSD O'Brien Core Center for Acute Kidney Injury ResearchP30DK079337 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI AGARWAL, ANUPAM · 2008 to 2022
$18.3M
San Diego EXPORT Comprehensive NCMHD Research CenterP60MD000220 · NIMHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DALEY, SANDRA P · 2002 to 2011
$11.0M
Predicting Risk of Human Leptospiros by Environmental SurveillanceR01AI108276 · NIAID · YALE UNIVERSITY · PI VINETZ, JOSEPH M. · 2013 to 2017
$3.6M
Patient-Oriented Research in Tropical Infectious DiseasesK24AI068903 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI VINETZ, JOSEPH M. · 2006 to 2015
$1.5M
NIAID NIH HHS K24 AI068903NIAID NIH HHS K24AI068903NIAID NIH HHS R01 AI108276NIAID NIH HHS R01AI108276NIDDK NIH HHS 1P30 DK 079337NIDDK NIH HHS P30 DK079337NIMHD NIH HHS P60 MD000220
6 · The paper itself

Abstract

backgroundInfectious Leptospira colonize the kidneys of reservoir (e.g. rats) and accidental hosts such as humans. The renal response to persistent leptospiral colonization, as measured by urinary protein biosignatures, has not been systematically studied. Urinary exosomes--bioactive membrane-bound nanovesicles--contain cell-state specific cargo that additively reflect formation all along the nephron. We hypothesized that Leptospira-infection will alter the content of urine exosomes, and further, that these Leptospira-induced alterations will hold clues to unravel novel pathways related to bacterial-host interactions. METHODOLOGY/PRINCIPAL

findingsExosome protein content from 24 hour urine samples of Leptospira-infected rats was compared with that of uninfected rats using SDS-PAGE and liquid chromatography/tandem mass spectrometry (LC-MS/MS). Statistical models were used to identify significantly dysregulated proteins in Leptospira-infected and uninfected rat urine exosomes. In all, 842 proteins were identified by LC-MS/MS proteomics of total rat urine and 204 proteins associated specifically with exosomes. Multivariate analysis showed that 25 proteins significantly discriminated between uninfected control and infected rats. Alanyl (membrane) aminopeptidase, also known as CD13 topped this list with the highest score, a finding we validated by Western immunoblotting. Whole urine analysis showed Tamm-Horsfall protein level reduction in the infected rat urine. Total urine and exosome proteins were significantly different in male vs. female infected rats.

conclusionsWe identified exosome-associated renal tubule-specific responses to Leptospira infection in a rat chronic colonization model. Quantitative differences in infected male and female rat urine exosome proteins vs. uninfected controls suggest that urine exosome analysis identifies important differences in kidney function that may be of clinical and pathological significance.

Indexed as

AnimalsBlotting, WesternChromatography, LiquidElectrophoresis, Polyacrylamide GelExosomesFemaleHost-Pathogen InteractionsKidney TubulesLeptospirosisMaleModels, StatisticalMultivariate AnalysisProteinuriaProteomicsRatsSex Factors

Identifiers

PMID25793258
PMCPMC4368819
OpenAlexW2070093265

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.