Glomerular permeability is not affected by heparan sulfate glycosaminoglycan deficiency in zebrafish embryos
| Autor: | Cristina Avramut, Jan A. Bruijn, Herman P. Spaink, Abraham J. Koster, Ramzi Khalil, Hans J. Baelde, Malgorzata Wiweger, Reshma A. Lalai, Pancras C.W. Hogendoorn |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Embryo Nonmammalian Physiology Kidney Glomerulus urologic and male genital diseases N-Acetylglucosaminyltransferases Glycosaminoglycan 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Zebrafish Proteinuria biology Chemistry urogenital system Glomerular basement membrane Glomerular permeability Heparan sulfate Zebrafish Proteins biology.organism_classification female genital diseases and pregnancy complications Cell biology carbohydrates (lipids) 030104 developmental biology medicine.anatomical_structure glomerular basement membrane Gene Expression Regulation glomerular filtration barrier 030220 oncology & carcinogenesis Mutation Glomerular Filtration Barrier heparan sulfate Heparitin Sulfate medicine.symptom proteinuria Function (biology) |
| Zdroj: | American Journal of Physiology-Renal Physiology, 317(5), F1211-F1216. AMER PHYSIOLOGICAL SOC American Journal of Physiology-Renal Physiology, 317(5), F1211-F1216 |
| ISSN: | 1522-1466 |
| Popis: | Proteinuria develops when specific components in the glomerular filtration barrier have impaired function. Although the precise components involved in maintaining this barrier have not been fully identified, heparan sulfate proteoglycans are believed to play an essential role in maintaining glomerular filtration. Although in situ studies have shown that a loss of heparan sulfate glycosaminoglycans increases the permeability of the glomerular filtration barrier, recent studies using experimental models have shown that podocyte-specific deletion of heparan sulfate glycosaminoglycan assembly does not lead to proteinuria. However, tubular reabsorption of leaked proteins might have masked an increase in glomerular permeability in these models. Furthermore, not only podocytes but also glomerular endothelial cells are involved in heparan sulfate synthesis in the glomerular filtration barrier. Therefore, we investigated the effect of a global heparan sulfate glycosaminoglycan deficiency on glomerular permeability. We used a zebrafish embryo model carrying a homozygous germline mutation in the ext2 gene. Glomerular permeability was assessed with a quantitative dextran tracer injection method. In this model, we accounted for tubular reabsorption. Loss of anionic sites in the glomerular basement membrane was measured using polyethyleneimine staining. Although mutant animals had significantly fewer negatively charged areas in the glomerular basement membrane, glomerular permeability was unaffected. Moreover, heparan sulfate glycosaminoglycan-deficient embryos had morphologically intact podocyte foot processes. Glomerular filtration remains fully functional despite a global reduction of heparan sulfate. |
| Databáze: | OpenAIRE |
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