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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2015

Open Access 01-12-2015 | Research

Differential urinary glycoproteome analysis of type 2 diabetic nephropathy using 2D-LC–MS/MS and iTRAQ quantification

Authors: Zhengguang Guo, Xuejiao Liu, Menglin Li, Chen Shao, Jianling Tao, Wei Sun, Mingxi Li

Published in: Journal of Translational Medicine | Issue 1/2015

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Abstract

Background

Diabetic nephropathy (DN) is the leading cause of chronic kidney failure and end-stage kidney disease. More accurate and non-invasive test for the diagnosis and monitoring the progression of DN is urgently needed for the better care of such patients.

Methods

In this study we utilized urinary glycoproteome to discover the differential proteins during the course of type 2 DN. The urinary glycoproteins from normal controls, normalbuminuira, microalbuminura, and macroalbuminuria patients were enriched by concanavalin A (ConA) and analyzed by 2DLC/MS/MS and isobaric tags for relative and absolute quantitation quantification.

Results

A total of 478 proteins were identified and 408 were annotated as N-linked glycoproteins. A total of 72, 107 and 123 differential proteins were identified in normalbuminuria, microalbuminuria and macroalbuminuria, respectively. By bioinformatics analysis, in normalbuminruia state, cell proliferation and cell movement were activated, which might reflect the compensatory phase during the disease development. In micro- and macro-albuminuria, cell death and apoptosis was activated, which might reflect the de-compensatory phase. Pathway analysis showed acute phase proteins, the member of high density lipoprotein and low density lipoprotein proteins were changed, indicating the role of the inflammatory response and lipid metabolism abnormality in the pathogenesis of DN. Six selected differential proteins were validated by Western Blot. Alpha-1-antitrypsin (SERPINA1) and Ceruloplasmin are the two markers with excellent area under curve values (0.929 and 1.000 respectively) to distinguish the microalbuminuria and normalbuminuria. For the first time, we found pro-epidermal growth factor and prolactin-inducible protein were decreased in macroalbuminuria stage, which might reflect the inhibition of cell viability and the activation of cell death in kidney.

Conclusions

Above data indicated that urinary glycoproteome could be useful to distinguish the differences in protein profiles in different stages in DN, which will help better individualized care of patients in DN.
Appendix
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Metadata
Title
Differential urinary glycoproteome analysis of type 2 diabetic nephropathy using 2D-LC–MS/MS and iTRAQ quantification
Authors
Zhengguang Guo
Xuejiao Liu
Menglin Li
Chen Shao
Jianling Tao
Wei Sun
Mingxi Li
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2015
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-015-0712-9

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