Altered O-glycomes of Renal Brush-Border Membrane in Model Rats with Chronic Kidney Diseases.

Aiying Yu,Junyao Wang,Jieqiang Zhong,Jingfu Zhao,Mark C Wagner,Yehia Mechref,Bruce A Molitoris,Shiv Pratap S Yadav

doi:10.3390/biom11111560

Aiying Yu, Junyao Wang + Show 6 more

Open Access

https://doi.org/10.3390/biom11111560

Copy DOI

Abstract

Chronic kidney disease (CKD) is defined as a decrease in renal function or glomerular filtration rate (GFR), and proteinuria is often present. Proteinuria increases with age and can be caused by glomerular and/or proximal tubule (PT) alterations. PT cells have an apical brush border membrane (BBM), which is a highly dynamic, organized, and specialized membrane region containing multiple glycoproteins required for its functions including regulating uptake, secretion, and signaling dependent upon the physiologic state. PT disorders contribute to the dysfunction observed in CKD. Many glycoprotein functions have been attributed to their N- and O-glycans, which are highly regulated and complex. In this study, the O-glycans present in rat BBMs from animals with different levels of kidney disease and proteinuria were characterized and analyzed using liquid chromatography tandem mass spectrometry (LC–MS/MS). A principal component analysis (PCA) documented that each group has distinct O-glycan distributions. Higher fucosylation levels were observed in the CKD and diabetic groups, which may contribute to PT dysfunction by altering physiologic glycoprotein interactions. Fucosylated O-glycans such as 1-1-1-0 exhibited higher abundance in the severe proteinuric groups. These glycomic results revealed that differential O-glycan expressions in CKD progressions has the potential to define the mechanism of proteinuria in kidney disease and to identify potential therapeutic interventions.

Highlights

Glycosylation is one of the most prevalent post-translational modifications in eukaryotes that impacts protein, lipid, and possibly RNA structure and function [1]
Along with the different glycan expressions in the group with proteinuria and hypertension, we investigated the glycan expression changes that might be associated with obesity and diabetes
Hypertension, obesity, and diabetes exhibited distinguishable O-glycan expressions compared with the two control groups

Summary

Introduction

Glycosylation is one of the most prevalent post-translational modifications in eukaryotes that impacts protein, lipid, and possibly RNA structure and function [1]. Numerous biological functions such as cell–cell signaling, cell–cell communication, protein targeting, inflammatory response, and immune response are associated with protein glycosylation [2,3,4,5,6]. The importance of protein glycosylation has been demonstrated in the progression of many human diseases, including liver diseases [7,8], neurological diseases, [9] Alzheimer’s disease [10,11], inflammatory diseases [12,13], and cancers [14,15,16,17,18,19]. It has been reported that O-glycan alterations were observed in the diabetic ovarian tissues of mouse and gastric cancer patients compared with healthy controls [24,25]

Methods

Results

Discussion

Conclusion