Dataset Information

Large-Scale Proteomic Assessment of Urinary Extracellular Vesicles Highlights Their Reliability in Reflecting Protein Changes in the Kidney.

ABSTRACT:

Background

Urinary extracellular vesicles (uEVs) are secreted into urine by cells from the kidneys and urinary tract. Although changes in uEV proteins are used for quantitative assessment of protein levels in the kidney or biomarker discovery, whether they faithfully reflect (patho)physiologic changes in the kidney is a matter of debate.

Methods

Mass spectrometry was used to compare in an unbiased manner the correlations between protein levels in uEVs and kidney tissue from the same animal. Studies were performed on rats fed a normal or high K⁺ diet.

Results

Absolute quantification determined a positive correlation (Pearson R=0.46 or 0.45, control or high K⁺ respectively, P<0.0001) between the approximately 1000 proteins identified in uEVs and corresponding kidney tissue. Transmembrane proteins had greater positive correlations relative to cytoplasmic proteins. Proteins with high correlations (R>0.9), included exosome markers Tsg101 and Alix. Relative quantification highlighted a monotonic relationship between altered transporter/channel abundances in uEVs and the kidney after dietary K⁺ manipulation. Analysis of genetic mouse models also revealed correlations between uEVs and kidney.

Conclusion

This large-scale unbiased analysis identifies uEV proteins that track the abundance of the parent proteins in the kidney. The data form a novel resource for the kidney community and support the reliability of using uEV protein changes to monitor specific physiologic responses and disease mechanisms.

SUBMITTER: Wu Q

PROVIDER: S-EPMC8729841 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

Large-Scale Proteomic Assessment of Urinary Extracellular Vesicles Highlights Their Reliability in Reflecting Protein Changes in the Kidney.

Wu Qi Q Poulsen Søren B SB Murali Sathish K SK Grimm Paul R PR Su Xiao-Tong XT Delpire Eric E Welling Paul A PA Ellison David H DH Ellison David H DH Fenton Robert A RA Fenton Robert A RA

Journal of the American Society of Nephrology : JASN 20210706 9

<h4>Background</h4>Urinary extracellular vesicles (uEVs) are secreted into urine by cells from the kidneys and urinary tract. Although changes in uEV proteins are used for quantitative assessment of protein levels in the kidney or biomarker discovery, whether they faithfully reflect (patho)physiologic changes in the kidney is a matter of debate.<h4>Methods</h4>Mass spectrometry was used to compare in an unbiased manner the correlations between protein levels in uEVs and kidney tissue from the sa ...[more]

PMID: 34230103

Similar Datasets

Project description:IntroductionTo better define the biological machinery associated with BK virus (BKV) infection, in kidney transplantation, we performed a proteomics analysis of urinary extracellular vesicles (EVs).MethodsTwenty-nine adult kidney transplant recipients (KTRs) with normal allograft function affected by BKV infection (15 with only viremia, 14 with viruria and viremia) and 15 controls (CTR, KTRs without BKV infection) were enrolled and randomly divided in a training cohort (12 BKV and 6 CTR) used for the mass spectrometry analysis of the EVs (microvesicles and exosomes) protein content and a testing cohort (17 BKV and 9 CTR) used for the biological validation of the proteomic results by ELISA. Bioinformatics and functional analysis revealed that several biological processes were enriched in BKV (including immunity, complement activation, renal fibrosis) and were able to discriminate BKV vs. CTR. Kinase was the only gene ontology annotation term including proteins less abundant in BKV (with SLK being the most significantly down-regulated protein). Non-linear support vector machine (SVM) learning and partial least squares discriminant analysis (PLS-DA) identified 36 proteins (including DNASE2, F12, AGT, CTSH, C4A, C7, FABP4, and BPNT1) able to discriminate the two study groups. The proteomic profile of KTRs with BKV viruria alone vs. viremia and viruria was quite similar. Enzyme-linked immunosorbent assay (ELISA) for SLK, BPNT1 and DNASE2, performed on testing cohort, validated proteomics results.DiscussionsOur pilot study demonstrated, for the first time, that BKV infection, also in the viruric state, can have a negative impact on the allograft and it suggested that, whether possible, an early preventive therapeutic strategy should be undertaken also in KTRs with viruria only. Our results, then, revealed new mechanistic insights into BKV infection and they selected potential biomarkers that should be tested in future studies with larger patients' cohorts.

Dataset Information

Large-Scale Proteomic Assessment of Urinary Extracellular Vesicles Highlights Their Reliability in Reflecting Protein Changes in the Kidney.

Background

Methods

Results

Conclusion

Publications

Large-Scale Proteomic Assessment of Urinary Extracellular Vesicles Highlights Their Reliability in Reflecting Protein Changes in the Kidney.

Similar Datasets

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