TY - JOUR
T1 - Changes in the expression of renal brush border membrane n-glycome in model rats with chronic kidney diseases
AU - Yu, Aiying
AU - Zhao, Jingfu
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 (1R01GM11-2490 (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 by a reduced renal function i.e., glomerular filtration rate (GFR), and the presence of kidney damage is determined by measurement of proteinuria or albuminuria. Albuminuria increases with age and can result from glomerular and/or proximal tubule (PT) alterations. Brush-border membranes (BBMs) on PT cells play an important role in maintaining the stability of PT functions. The PT BBM, a highly dynamic, organized, specialized membrane, contains a variety of glycoproteins required for the functions of PT. Since protein glycosylation regulates many protein functions, the alteration of glycosylation due to the glycan changes has attracted more interests for a variety of disease studies recently. In this work, liquid chromatography-tandem mass spectrometry was utilized to analyze the abundances of permethylated glycans from rats under control to mild CKD, severe CKD, and diabetic conditions. The most significant differences were observed in sialylation level with the highest present in the severe CKD and diabetic groups. Moreover, high mannose N-glycans was enriched in the CKD BBMs. Characterization of all the BBM N-glycan changes supports that these changes are likely to impact the functional properties of the dynamic PT BBM. Further, these changes may lead to the potential discovery of glycan biomarkers for improved CKD diagnosis and new avenues for therapeutic treatments.
AB - Chronic kidney disease (CKD) is defined by a reduced renal function i.e., glomerular filtration rate (GFR), and the presence of kidney damage is determined by measurement of proteinuria or albuminuria. Albuminuria increases with age and can result from glomerular and/or proximal tubule (PT) alterations. Brush-border membranes (BBMs) on PT cells play an important role in maintaining the stability of PT functions. The PT BBM, a highly dynamic, organized, specialized membrane, contains a variety of glycoproteins required for the functions of PT. Since protein glycosylation regulates many protein functions, the alteration of glycosylation due to the glycan changes has attracted more interests for a variety of disease studies recently. In this work, liquid chromatography-tandem mass spectrometry was utilized to analyze the abundances of permethylated glycans from rats under control to mild CKD, severe CKD, and diabetic conditions. The most significant differences were observed in sialylation level with the highest present in the severe CKD and diabetic groups. Moreover, high mannose N-glycans was enriched in the CKD BBMs. Characterization of all the BBM N-glycan changes supports that these changes are likely to impact the functional properties of the dynamic PT BBM. Further, these changes may lead to the potential discovery of glycan biomarkers for improved CKD diagnosis and new avenues for therapeutic treatments.
KW - Brush-border membrane
KW - Chronic kidney disease
KW - Glycomics
KW - LC-MS/MS
KW - Obese and diabetic
KW - Proteinuria and hypertension
UR - http://www.scopus.com/inward/record.url?scp=85118745683&partnerID=8YFLogxK
U2 - 10.3390/biom11111677
DO - 10.3390/biom11111677
M3 - Article
C2 - 34827675
AN - SCOPUS:85118745683
SN - 2218-273X
VL - 11
JO - Biomolecules
JF - Biomolecules
IS - 11
M1 - 1677
ER -