title: Glycosylation patterns of kidney proteins differ in rat diabetic nephropathy.
abstract: Diabetic nephropathy often progresses to end-stage kidney disease and, ultimately, to renal replacement therapy. Hyperglycemia per se is expected to have a direct impact on the biosynthesis of N- and O-linked glycoproteins. This study aims to establish the link between protein glycosylation and progression of experimental diabetic kidney disease using orthogonal methods. Kidneys of streptozotocin-diabetic and control rats were harvested at three different time points post streptozotocin injection. A panel of 12 plant lectins was used in the screening of lectin blots. The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. Lectin affinity chromatography followed by mass spectrometric analyses led to the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation. Our data confirm a substantial link between glycosylation signature and diabetes progression. Furthermore, as suggested by our findings on dipeptidyl peptidase-IV, altered protein glycosylation may reflect changes in biochemical properties such as enzymatic activity. Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease.
authors.affiliation: Centre for BioAnalytical Sciences, Dublin City University, Dublin, Ireland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ravidà
authors.affiliation: Centre for BioAnalytical Sciences, Dublin City University, Dublin, Ireland.
authors.forename: Luca
authors.initials: L
authors.lastname: Musante
authors.affiliation: Centre for BioAnalytical Sciences, Dublin City University, Dublin, Ireland.
authors.forename: Marjut
authors.initials: M
authors.lastname: Kreivi
authors.affiliation: Centre for BioAnalytical Sciences, Dublin City University, Dublin, Ireland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Miinalainen
authors.affiliation: Centre for BioAnalytical Sciences, Dublin City University, Dublin, Ireland.
authors.forename: Barry
authors.initials: B
authors.lastname: Byrne
authors.affiliation: Centre for BioAnalytical Sciences, Dublin City University, Dublin, Ireland.
authors.forename: Mayank
authors.initials: M
authors.lastname: Saraswat
authors.affiliation: National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Henry
authors.affiliation: National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
authors.forename: Paula
authors.initials: P
authors.lastname: Meleady
authors.affiliation: National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
authors.forename: Martin
authors.initials: M
authors.lastname: Clynes
authors.affiliation: Centre for BioAnalytical Sciences, Dublin City University, Dublin, Ireland.
authors.forename: Harry
authors.initials: H
authors.lastname: Holthofer
mesh_terms: D000818:Animals; D003928:Diabetic Nephropathies / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D018450:Disease Progression; D006031:Glycosylation; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D037121:Plant Lectins; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
chemical_list: D037121:Plant Lectins; D013311:Streptozocin; D018819:Dipeptidyl Peptidase 4