Regulated secretion and role of urinary nanovesicles

Projektinformationen

Exosomes

ID Finanzhilfevereinbarung: 705862

DOI

10.3030/705862

Projekt abgeschlossen

EK-Unterschriftsdatum 23 Februar 2016

Startdatum 1 September 2017

Enddatum 31 August 2019

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten

€ 200 194,80

EU-Beitrag

€ 200 194,80

Koordiniert durch

AARHUS UNIVERSITET
Denmark

Periodic Reporting for period 1 - Exosomes (Regulated secretion and role of urinary nanovesicles)

Berichtszeitraum: 2017-09-01 bis 2019-08-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Kidney disease, and its associated diabetes or high blood pressure, pose a great health risk for millions of people worldwide. The kidneys are part of the urinary tract that produces urine. Therefore, urine contains potential substances that can indicate the (patho)physiological conditions of the kidney.
The purpose of this project is to examine the contents and role of the secreted urinary nanovesicles, in particular, exosomes, under different (patho)physiological conditions, with the hope of finding potential biomarkers from urinary exosomes. We have employed a transdisciplinary approach where multiple techniques including proteomics, bioinformatics and cell biology were used. Overall, we have revealed a proteome-scale positive correlation between urinary exosomes and kidney, indicating that urinary exosomes could reflect the physiological changes in the kidney to some extent. We also generated a comprehensive proteome database on urinary exosomes and kidney under different (patho)physiological conditions, facilitating targeted biomarker discovery.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

First, we confirmed our hypothesis that deubiquitylation of protein cargo is not an essential step in exosome formation. Then a proteome-scale comparison between rat urinary exosomes and kidney revealed a positive correlation, suggesting that urinary exosomes could reflect the physiological changes in the kidney to some extent. Furthermore, we investigated the effects of four pathophysiological conditions on rat urinary exosomes and kidney, mimicked by four different diets, and generated a comprehensive proteome database under different pathophysiological conditions that could facilitate targeted biomarker discovery. The final work package involving patient samples has evolved into a much bigger collaborative project, where experiments on human urinary exosomes from patients with primary aldosteronism are underway, aiming at finding new therapeutic targets to control or even prevent hypertension. During the duration of the project, I have been invited or selected to give talks at international scientific conferences.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

Although researchers have been using urinary proteome to study kidney, whether a correlation exists between the levels of proteins in the urine and their corresponding levels in kidney tissue has never been comprehensively determined. We, to the best of our knowledge, did the first proteome-scale comparison between urine and kidney, and revealed a positive correlation. This finding sets the theoretical grounding for the exploitation of urinary exosomes as a surrogate to assess kidney function.