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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| Format: | Article |
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Nature Portfolio
2021-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-87753-3 |
| _version_ | 1828973386403938304 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T13:44:38Z |
| format | Article |
| id | doaj.art-893469d74f4a4c3aa2e23c7c29efebb4 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T13:44:38Z |
| publishDate | 2021-04-01 |
| publisher | Nature Portfolio |
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| spelling | doaj.art-893469d74f4a4c3aa2e23c7c29efebb42022-12-21T22:59:21ZengNature PortfolioScientific Reports2045-23222021-04-0111111210.1038/s41598-021-87753-3Proteoglycans contribute to the functional integrity of the glomerular endothelial cell surface layer and are regulated in diabetic kidney diseaseAlina Khramova0Roberto Boi1Vincent Fridén2Anna Björnson Granqvist3Ulf Nilsson4Olav Tenstad5Eystein Oveland6Börje Haraldsson7Kerstin Ebefors8Jenny Nyström9Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of GothenburgInstitute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of GothenburgInstitute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of GothenburgInstitute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of GothenburgInstitute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of GothenburgDepartment of Biomedicine, University of BergenDepartment of Biomedicine, University of BergenInstitute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of GothenburgInstitute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of GothenburgInstitute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of GothenburgAbstract 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.https://doi.org/10.1038/s41598-021-87753-3 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-87753-3 |
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