TY - JOUR
T1 - Altered o-glycomes of renal brush-border membrane in model rats with chronic kidney diseases
AU - Yu, Aiying
AU - Zhao, Jingfu
AU - Zhong, Jieqiang
AU - Wang, Junyao
AU - Yadav, Shiv Pratap S.
AU - Molitoris, Bruce A.
AU - Wagner, Mark C.
AU - Mechref, Yehia
N1 - Funding Information:
Funding: This research was supported by grants from National Institutes of Health NIH (1R01GM112 490 (YM), 1R01GM130091(YM), P30DK079312-13 (BAM), and 1R01DK091623-06 (BAM)).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - Brush-border membrane
KW - Chronic kidney disease
KW - Differential expression analysis
KW - LC–MS/MS
KW - O-glycan
KW - Obese and diabetic
KW - Proteinuria and hypertension
UR - http://www.scopus.com/inward/record.url?scp=85117442434&partnerID=8YFLogxK
U2 - 10.3390/biom11111560
DO - 10.3390/biom11111560
M3 - Article
AN - SCOPUS:85117442434
VL - 11
JO - Biomolecules
JF - Biomolecules
SN - 2218-273X
IS - 11
M1 - 1560
ER -