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- Fridén, Vincent, 1975, et al.
(författare)
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The glomerular endothelial cell coat is essential for glomerular filtration
- 2011
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Ingår i: Kidney international. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 79:12, s. 1322-1330
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Tidskriftsartikel (refereegranskat)abstract
- The endothelial cell surface layer (ESL) is believed to contribute to the glomerular barrier, and the nature of its molecular structure is still largely unknown. The ESL consists of the membrane-bound glycocalyx and the loosely attached endothelial cell coat (ECC). A brief injection of hypertonic sodium chloride into the left renal artery was used to displace, elute, and collect non-covalently bound components of the renal ESL in rats. This procedure increased the fractional clearance of albumin 12-fold without detectable morphological changes as assessed by electron microscopy compared with the control group injected with isotonic saline. Mathematical modeling suggested a reduced glomerular charge density. Mass spectrometry of the renal eluate identified 17 non-covalently bound proteins normally present in the ECC. One of these proteins, orosomucoid, has previously been shown to be important for capillary permselectivity. Another protein, lumican, is expressed by glomerular endothelial cells and likely contributes to maintaining an intact barrier. Thus, the absence of one or more of these proteins causes proteinuria and illustrates the importance of the ECC in glomerular permselectivity.Kidney International advance online publication, 16 March 2011; doi:10.1038/ki.2011.58.
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| 2. |
- Khramova, Alina, 1989, et al.
(författare)
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Proteoglycans contribute to the functional integrity of the glomerular endothelial cell surface layer and are regulated in diabetic kidney disease
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)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 1M 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. © 2021, The Author(s).
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