Proteoglycans contribute to the functional integrity of the glomerular endothelial cell surface layer and are regulated in diabetic kidney disease

Abstract All capillary endothelia, including those of the glomeruli, have a luminal cell surface layer (ESL) consisting of glycoproteins, glycolipids, proteoglycans (PGs) and glycosaminoglycans. Previous results have demonstrated that an intact ESL is necessary for a normal filtration barrier and da...

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Autores principales:	Alina Khramova, Roberto Boi, Vincent Fridén, Anna Björnson Granqvist, Ulf Nilsson, Olav Tenstad, Eystein Oveland, Börje Haraldsson, Kerstin Ebefors, Jenny Nyström
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/893469d74f4a4c3aa2e23c7c29efebb4
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spelling	oai:doaj.org-article:893469d74f4a4c3aa2e23c7c29efebb42021-12-02T17:32:58ZProteoglycans contribute to the functional integrity of the glomerular endothelial cell surface layer and are regulated in diabetic kidney disease10.1038/s41598-021-87753-32045-2322https://doaj.org/article/893469d74f4a4c3aa2e23c7c29efebb42021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87753-3https://doaj.org/toc/2045-2322Abstract All capillary endothelia, including those of the glomeruli, have a luminal cell surface layer (ESL) consisting of glycoproteins, glycolipids, proteoglycans (PGs) and glycosaminoglycans. Previous results have demonstrated that an intact ESL is necessary for a normal filtration barrier and damage to the ESL coupled to proteinuria is seen for example in diabetic kidney disease (DKD). We used the principles of ion exchange chromatography in vivo to elute the highly negatively charged components of the ESL with a 1 M NaCl solution in rats. Ultrastructural morphology and renal function were analyzed and 17 PGs and hyaluronan were identified in the ESL. The high salt solution reduced the glomerular ESL thickness, led to albuminuria and reduced GFR. To assess the relevance of ESL in renal disease the expression of PGs in glomeruli from DKD patients in a next generation sequencing cohort was investigated. We found that seven of the homologues of the PGs identified in the ESL from rats were differently regulated in patients with DKD compared to healthy subjects. The results show that proteoglycans and glycosaminoglycans are essential components of the ESL, maintaining the permselective properties of the glomerular barrier and thus preventing proteinuria.Alina KhramovaRoberto BoiVincent FridénAnna Björnson GranqvistUlf NilssonOlav TenstadEystein OvelandBörje HaraldssonKerstin EbeforsJenny NyströmNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alina Khramova Roberto Boi Vincent Fridén Anna Björnson Granqvist Ulf Nilsson Olav Tenstad Eystein Oveland Börje Haraldsson Kerstin Ebefors Jenny Nyström Proteoglycans contribute to the functional integrity of the glomerular endothelial cell surface layer and are regulated in diabetic kidney disease
description	Abstract All capillary endothelia, including those of the glomeruli, have a luminal cell surface layer (ESL) consisting of glycoproteins, glycolipids, proteoglycans (PGs) and glycosaminoglycans. Previous results have demonstrated that an intact ESL is necessary for a normal filtration barrier and damage to the ESL coupled to proteinuria is seen for example in diabetic kidney disease (DKD). We used the principles of ion exchange chromatography in vivo to elute the highly negatively charged components of the ESL with a 1 M NaCl solution in rats. Ultrastructural morphology and renal function were analyzed and 17 PGs and hyaluronan were identified in the ESL. The high salt solution reduced the glomerular ESL thickness, led to albuminuria and reduced GFR. To assess the relevance of ESL in renal disease the expression of PGs in glomeruli from DKD patients in a next generation sequencing cohort was investigated. We found that seven of the homologues of the PGs identified in the ESL from rats were differently regulated in patients with DKD compared to healthy subjects. The results show that proteoglycans and glycosaminoglycans are essential components of the ESL, maintaining the permselective properties of the glomerular barrier and thus preventing proteinuria.
format	article
author	Alina Khramova Roberto Boi Vincent Fridén Anna Björnson Granqvist Ulf Nilsson Olav Tenstad Eystein Oveland Börje Haraldsson Kerstin Ebefors Jenny Nyström
author_facet	Alina Khramova Roberto Boi Vincent Fridén Anna Björnson Granqvist Ulf Nilsson Olav Tenstad Eystein Oveland Börje Haraldsson Kerstin Ebefors Jenny Nyström
author_sort	Alina Khramova
title	Proteoglycans contribute to the functional integrity of the glomerular endothelial cell surface layer and are regulated in diabetic kidney disease
title_short	Proteoglycans contribute to the functional integrity of the glomerular endothelial cell surface layer and are regulated in diabetic kidney disease
title_full	Proteoglycans contribute to the functional integrity of the glomerular endothelial cell surface layer and are regulated in diabetic kidney disease
title_fullStr	Proteoglycans contribute to the functional integrity of the glomerular endothelial cell surface layer and are regulated in diabetic kidney disease
title_full_unstemmed	Proteoglycans contribute to the functional integrity of the glomerular endothelial cell surface layer and are regulated in diabetic kidney disease
title_sort	proteoglycans contribute to the functional integrity of the glomerular endothelial cell surface layer and are regulated in diabetic kidney disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/893469d74f4a4c3aa2e23c7c29efebb4
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Proteoglycans contribute to the functional integrity of the glomerular endothelial cell surface layer and are regulated in diabetic kidney disease

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