Abstract
BackgroundDiabetic 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.MethodsIn 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.ResultsA 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.ConclusionsAbove 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0712-9) contains supplementary material, which is available to authorized users.
Highlights
Diabetic nephropathy (DN) is the leading cause of chronic kidney failure and end-stage kidney disease
Qualitative and quantitative analysis of urinary glycoproteome Three group diabetic patients were included in this study, normoalbuminuria group, microalbuminuria group and macroalbuminuria group
By function and pathway analysis, we found that cell necrosis were inhibited and cell movement and cell proliferation were activated in diabetes mellitus (DM), while on the contrary, Fig. 7 Western blot validation for six differential proteins
Summary
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. A simple, accurate and non-invasive test was urgently needed for early diagnosis of DN and/or monitoring its progression [5]. As many as 55–70 % microalbuminuria patients do not progress to proteinuria within 10 years, while ~40 % of those who are at risk of progression to proteinuria are constantly normoalbuminura [6]. This calls for more accurate biomarkers in clinical research and its application
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