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Regulated secretion and role of urinary nanovesicles

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

Okres sprawozdawczy: 2017-09-01 do 2019-08-31

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.
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.
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.