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

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),...

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Autores principales: Aiying Yu, Jingfu Zhao, Jieqiang Zhong, Junyao Wang, Shiv Pratap S. Yadav, Bruce A. Molitoris, Mark C. Wagner, Yehia Mechref
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:bbd8f5c80fb74ce9bf556ae79c00c53e2021-11-25T16:51:52ZAltered <i>O</i>-glycomes of Renal Brush-Border Membrane in Model Rats with Chronic Kidney Diseases10.3390/biom111115602218-273Xhttps://doaj.org/article/bbd8f5c80fb74ce9bf556ae79c00c53e2021-10-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1560https://doaj.org/toc/2218-273XChronic 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 <i>N</i>- and <i>O</i>-glycans, which are highly regulated and complex. In this study, the <i>O</i>-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 <i>O</i>-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 <i>O</i>-glycans such as 1-1-1-0 exhibited higher abundance in the severe proteinuric groups. These glycomic results revealed that differential <i>O</i>-glycan expressions in CKD progressions has the potential to define the mechanism of proteinuria in kidney disease and to identify potential therapeutic interventions.Aiying YuJingfu ZhaoJieqiang ZhongJunyao WangShiv Pratap S. YadavBruce A. MolitorisMark C. WagnerYehia MechrefMDPI AGarticle<i>O</i>-glycanbrush-border membraneproteinuria and hypertensionobese and diabeticchronic kidney diseasedifferential expression analysisMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1560, p 1560 (2021)
institution DOAJ
collection DOAJ
language EN
topic <i>O</i>-glycan
brush-border membrane
proteinuria and hypertension
obese and diabetic
chronic kidney disease
differential expression analysis
Microbiology
QR1-502
spellingShingle <i>O</i>-glycan
brush-border membrane
proteinuria and hypertension
obese and diabetic
chronic kidney disease
differential expression analysis
Microbiology
QR1-502
Aiying Yu
Jingfu Zhao
Jieqiang Zhong
Junyao Wang
Shiv Pratap S. Yadav
Bruce A. Molitoris
Mark C. Wagner
Yehia Mechref
Altered <i>O</i>-glycomes of Renal Brush-Border Membrane in Model Rats with Chronic Kidney Diseases
description 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 <i>N</i>- and <i>O</i>-glycans, which are highly regulated and complex. In this study, the <i>O</i>-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 <i>O</i>-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 <i>O</i>-glycans such as 1-1-1-0 exhibited higher abundance in the severe proteinuric groups. These glycomic results revealed that differential <i>O</i>-glycan expressions in CKD progressions has the potential to define the mechanism of proteinuria in kidney disease and to identify potential therapeutic interventions.
format article
author Aiying Yu
Jingfu Zhao
Jieqiang Zhong
Junyao Wang
Shiv Pratap S. Yadav
Bruce A. Molitoris
Mark C. Wagner
Yehia Mechref
author_facet Aiying Yu
Jingfu Zhao
Jieqiang Zhong
Junyao Wang
Shiv Pratap S. Yadav
Bruce A. Molitoris
Mark C. Wagner
Yehia Mechref
author_sort Aiying Yu
title Altered <i>O</i>-glycomes of Renal Brush-Border Membrane in Model Rats with Chronic Kidney Diseases
title_short Altered <i>O</i>-glycomes of Renal Brush-Border Membrane in Model Rats with Chronic Kidney Diseases
title_full Altered <i>O</i>-glycomes of Renal Brush-Border Membrane in Model Rats with Chronic Kidney Diseases
title_fullStr Altered <i>O</i>-glycomes of Renal Brush-Border Membrane in Model Rats with Chronic Kidney Diseases
title_full_unstemmed Altered <i>O</i>-glycomes of Renal Brush-Border Membrane in Model Rats with Chronic Kidney Diseases
title_sort altered <i>o</i>-glycomes of renal brush-border membrane in model rats with chronic kidney diseases
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/bbd8f5c80fb74ce9bf556ae79c00c53e
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