Deciphering the disease-related molecular networks using urine proteomics

Abstract

Despite the large number of studies focused on the impact of diseases on urine proteome, few outputs with clinical meaning were retrieved so far. The goal of this study was to identify the biological processes modulated in urine by distinct diseases to better understand disease pathogenesis and to identify urinary proteins with potential diagnosis value. We searched PubMed and SCOPUS databases for mass spectrometry-based experimental papers and pooled differentially expressed proteins by disease and target organic system. A total of 2572 differentially expressed proteins or peptides were pooled from 89 studies focused on 57 diseases. Data analysis highlighted inflammation as a biological process modulated by all diseases. However, specific inflammatory signatures are associated with specific diseases and/or aetiologies. Moreover, specific biological processes were identified for specific groups of pathologies and unique proteins identified. Overall, integrative data analysis from urine proteomics/peptidomics reinforces the clinical potential of this body fluid for the clinical management of distinct diseases.

Digging Deep into Peptidomics Applied to Body Fluids

“…Urine is an attractive body fluid for clinical purposes as it can be collected in large volumes noninvasively without the concern of proteases activation . This body fluid contains water, salts, metabolites, and small amounts of proteins, which may originate in the blood or the urinary track itself.…”

“…Thus, urine can provide valuable information on systemic as well as local physiology . Several studies have been carried out to characterize the urinary proteome using MS‐based approaches (reviewed by ). This fluid also harbors a high number of naturally occurring peptides, with more than 5000 peptides reported so far (Figure and Supporting Information, Table S1).…”

“…This data analysis highlights the contribution of exosomes to body fluids proteome/peptidome. In the case of urine, exosomes seem to contribute in around 30% to whole fluid proteome . Urine specific native peptides are derived from proteins involved in the biological processes “collagen catabolic process”, “multicellular organismal catabolic process”, “extracellular matrix disassembly”, “extracellular matrix organization”, and “cell adhesion” (according to String v10.5), which illustrates the huge contribution of extracellular matrix to urine composition.…”

“…Changes in the collagen homeostasis were previously associated with the aging process and pathological conditions such as the cardiovascular diseases . Among the proteases that target extracellular matrix proteins, including collagens, is kallikrein‐6 …”