Proteases and Protease Inhibitors of Urinary Extracellular Vesicles in Diabetic Nephropathy

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Musante , L , Tataruch , D , Gu , D , Liu , X , Forsblom , C , Groop , P-H & Holthofer , H 2015 , ' Proteases and Protease Inhibitors of Urinary Extracellular Vesicles in Diabetic Nephropathy ' Journal of diabetes research . DOI: 10.1155/2015/289734

Title: Proteases and Protease Inhibitors of Urinary Extracellular Vesicles in Diabetic Nephropathy
Author: Musante, Luca; Tataruch, Dorota; Gu, Dongfeng; Liu, Xinyu; Forsblom, Carol; Groop, Per-Henrik; Holthofer, Harry
Contributor: University of Helsinki, Clinicum
University of Helsinki, Department of Medicine
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2015
Language: eng
Number of pages: 14
Belongs to series: Journal of diabetes research
ISSN: 2314-6745
URI: http://hdl.handle.net/10138/176381
Abstract: Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus (DM), leads to chronic kidney disease (CKD), and, ultimately, is the main cause for end-stage kidney disease (ESKD). Beyond urinary albumin, no reliable biomarkers are available for accurate early diagnostics. Urinary extracellular vesicles (UEVs) have recently emerged as an interesting source of diagnostic and prognostic disease biomarkers. Here we used a protease and respective protease inhibitor array to profile urines of type 1 diabetes patients at different stages of kidney involvement. Urine samples were divided into groups based on the level of albuminuria and UEVs isolated by hydrostatic dialysis and screened for relative changes of 34 different proteases and 32 protease inhibitors, respectively. Interestingly, myeloblastin and its natural inhibitor elafin showed an increase in the normo- and microalbuminuric groups. Similarly, a characteristic pattern was observed in the array of protease inhibitors, with a marked increase of cystatin B, natural inhibitor of cathepsins L, H, and B as well as of neutrophil gelatinase-associated Lipocalin (NGAL) in the normoalbuminuric group. This study shows for the first time the distinctive alterations in comprehensive protease profiles of UEVs in diabetic nephropathy and uncovers intriguing mechanistic, prognostic, and diagnostic features of kidney damage in diabetes.
Subject: GLOMERULAR ENDOTHELIAL-CELLS
DIPEPTIDYL PEPTIDASE-IV
CHRONIC KIDNEY-DISEASE
ALL-CAUSE MORTALITY
MATRIX METALLOPROTEINASES
CARDIOVASCULAR-DISEASE
PROTEINASE-3
EXOSOMES
APOPTOSIS
PROGRESSION
3121 Internal medicine
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