Cargando…

Changes in the Expression of Renal Brush Border Membrane N-Glycome in Model Rats with Chronic Kidney Diseases

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) alterati...

Descripción completa

Detalles Bibliográficos
Autores principales: Yu, Aiying, Zhao, Jingfu, Yadav, Shiv Pratap S., Molitoris, Bruce A., Wagner, Mark C., Mechref, Yehia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616023/
https://www.ncbi.nlm.nih.gov/pubmed/34827675
http://dx.doi.org/10.3390/biom11111677
_version_ 1784604247566843904
author Yu, Aiying
Zhao, Jingfu
Yadav, Shiv Pratap S.
Molitoris, Bruce A.
Wagner, Mark C.
Mechref, Yehia
author_facet Yu, Aiying
Zhao, Jingfu
Yadav, Shiv Pratap S.
Molitoris, Bruce A.
Wagner, Mark C.
Mechref, Yehia
author_sort Yu, Aiying
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8616023
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-86160232021-11-26 Changes in the Expression of Renal Brush Border Membrane N-Glycome in Model Rats with Chronic Kidney Diseases Yu, Aiying Zhao, Jingfu Yadav, Shiv Pratap S. Molitoris, Bruce A. Wagner, Mark C. Mechref, Yehia Biomolecules Article 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. MDPI 2021-11-11 /pmc/articles/PMC8616023/ /pubmed/34827675 http://dx.doi.org/10.3390/biom11111677 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yu, Aiying
Zhao, Jingfu
Yadav, Shiv Pratap S.
Molitoris, Bruce A.
Wagner, Mark C.
Mechref, Yehia
Changes in the Expression of Renal Brush Border Membrane N-Glycome in Model Rats with Chronic Kidney Diseases
title Changes in the Expression of Renal Brush Border Membrane N-Glycome in Model Rats with Chronic Kidney Diseases
title_full Changes in the Expression of Renal Brush Border Membrane N-Glycome in Model Rats with Chronic Kidney Diseases
title_fullStr Changes in the Expression of Renal Brush Border Membrane N-Glycome in Model Rats with Chronic Kidney Diseases
title_full_unstemmed Changes in the Expression of Renal Brush Border Membrane N-Glycome in Model Rats with Chronic Kidney Diseases
title_short Changes in the Expression of Renal Brush Border Membrane N-Glycome in Model Rats with Chronic Kidney Diseases
title_sort changes in the expression of renal brush border membrane n-glycome in model rats with chronic kidney diseases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616023/
https://www.ncbi.nlm.nih.gov/pubmed/34827675
http://dx.doi.org/10.3390/biom11111677
work_keys_str_mv AT yuaiying changesintheexpressionofrenalbrushbordermembranenglycomeinmodelratswithchronickidneydiseases
AT zhaojingfu changesintheexpressionofrenalbrushbordermembranenglycomeinmodelratswithchronickidneydiseases
AT yadavshivprataps changesintheexpressionofrenalbrushbordermembranenglycomeinmodelratswithchronickidneydiseases
AT molitorisbrucea changesintheexpressionofrenalbrushbordermembranenglycomeinmodelratswithchronickidneydiseases
AT wagnermarkc changesintheexpressionofrenalbrushbordermembranenglycomeinmodelratswithchronickidneydiseases
AT mechrefyehia changesintheexpressionofrenalbrushbordermembranenglycomeinmodelratswithchronickidneydiseases