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

Biomolecules

Yehia Mechref¹  Jieqiang Zhong¹  Junyao Wang¹  Aiying Yu¹  Jingfu Zhao¹  Mark C. Wagner²  Bruce A. Molitoris²  Shiv Pratap S. Yadav² 

[1] Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USA;Department of Medicine, Nephrology Division, Indiana University, Indianapolis, IN 46202, USA;

关键词: O-glycan;    brush-border membrane;    proteinuria and hypertension;    obese and diabetic;    chronic kidney disease;    differential expression analysis;   

DOI  :  10.3390/biom11111560

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown