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Proteomic Analysis of Urinary Extracellular Vesicles Reveals a Role for the Complement System in Medullary Sponge Kidney Disease
- Source :
- International Journal of Molecular Sciences, Volume 20, Issue 21, International Journal of Molecular Sciences, Vol 20, Iss 21, p 5517 (2019)
- Publication Year :
- 2019
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2019.
-
Abstract
- Medullary sponge kidney (MSK) disease is a rare and neglected kidney condition often associated with nephrocalcinosis/nephrolithiasis and cystic anomalies in the precalyceal ducts. Little is known about the pathogenesis of this disease, so we addressed the knowledge gap using a proteomics approach. The protein content of microvesicles/exosomes isolated from urine of 15 MSK and 15 idiopathic calcium nephrolithiasis (ICN) patients was investigated by mass spectrometry, followed by weighted gene co-expression network analysis, support vector machine (SVM) learning, and partial least squares discriminant analysis (PLS-DA) to select the most discriminative proteins. Proteomic data were verified by ELISA. We identified 2998 proteins in total, 1764 (58.9%) of which were present in both vesicle types in both diseases. Among the MSK samples, only 65 (2.2%) and 137 (4.6%) proteins were exclusively found in the microvesicles and exosomes, respectively. Similarly, among the ICN samples, only 75 (2.5%) and 94 (3.1%) proteins were exclusively found in the microvesicles and exosomes, respectively. SVM learning and PLS-DA revealed a core panel of 20 proteins that distinguished extracellular vesicles representing each clinical condition with an accuracy of 100%. Among them, three exosome proteins involved in the lectin complement pathway maximized the discrimination between MSK and ICN: Ficolin 1, Mannan-binding lectin serine protease 2, and Complement component 4-binding protein &beta<br />ELISA confirmed the proteomic results. Our data show that the complement pathway is involved in the MSK, revealing a new range of potential therapeutic targets and early diagnostic biomarkers.
- Subjects :
- 0301 basic medicine
Adult
Male
idiopathic calcium nephrolithiasis
030232 urology & nephrology
Proteomics
Medullary sponge kidney
Exosomes
Nephrolithiasis
Exosome
Catalysis
Article
Inorganic Chemistry
lcsh:Chemistry
03 medical and health sciences
Extracellular Vesicles
0302 clinical medicine
medullary sponge kidney
proteomics
medicine
Humans
Physical and Theoretical Chemistry
Molecular Biology
lcsh:QH301-705.5
Spectroscopy
complement system
Serine protease
biology
Organic Chemistry
Lectin
Proteins
General Medicine
Complement System Proteins
medicine.disease
Molecular biology
Microvesicles
Computer Science Applications
Complement system
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
Female
Ficolin
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....9a8600e4bc62821ee79b07024b176b98
- Full Text :
- https://doi.org/10.3390/ijms20215517