Sulfatases, in Particular Sulf1, Are Important for the Integrity of the Glomerular Filtration Barrier in Zebrafish
Autor: | Michaela Beese, Hermann Haller, Patricia Schroder, Anna Masseli, Heiko Schenk, Patricia Bolanos-Palmieri, Jan Hinrich Bräsen, Jan Hegermann |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Morpholino Article Subject lcsh:Medicine General Biochemistry Genetics and Molecular Biology Gene Expression Regulation Enzymologic Morpholinos 03 medical and health sciences 0302 clinical medicine Glomerular Basement Membrane medicine Animals Zebrafish Kidney Gene knockdown General Immunology and Microbiology biology Chemistry Podocytes Glomerular basement membrane lcsh:R Endothelial Cells Gene Expression Regulation Developmental Morphant General Medicine Zebrafish Proteins biology.organism_classification Cell biology Pronephros 030104 developmental biology medicine.anatomical_structure Gene Knockdown Techniques Glomerular Filtration Barrier Sulfatases 030217 neurology & neurosurgery Research Article |
Zdroj: | BioMed Research International BioMed Research International, Vol 2019 (2019) |
ISSN: | 2314-6133 |
DOI: | 10.1155/2019/4508048 |
Popis: | The 6-O-endosulfatases (sulfs) are important enzymatic components involved in the regulation of heparan sulfate by altering the sulfatation pattern. Specifically in the kidney, sulfs have been implicated in the glomerular podocyte-endothelial cell crosstalk and in the preservation of the glomerular filtration barrier (GFB) in different mouse models. Since it has been shown that in zebrafish larvae, Sulf1, Sulf2a, and Sulf2b are expressed in the pronephric kidney we set out to establish if a reduction in sulf expression leads to GFB dysfunction. Here, we show that a reduced sulf expression following morpholino (MO) induced knockdown in zebrafish larvae promotes damage to the GFB leading to renal plasma protein loss from the circulation. Moreover, a combined knockdown of Sulf1, Sulf2a, and Sulf2b is associated with severe morphologic changes including narrowing of the fenestration between glomerular endothelial cells as well as thickening of the glomerular basement membrane and podocyte foot process effacement, suggesting that glomerular damage is an underlying cause of the circulatory protein loss observed after MO injection. Additionally, we show that a decrease in sulf expression reduces the bioavailability of VegfA in the glomerulus of the pronephros, which may contribute to the structural changes observed in the glomeruli of morphant fish. Furthermore, consistent with previous results, knockdown of the sulfs is associated with arteriovenous malformations in particular in the tail region of the larvae. Overall, taken together our results suggest that 6-O-endosulfatases are important in the preservation of GFB integrity and a reduction in their expression levels induces phenotypic changes that are indicative of renal protein loss. |
Databáze: | OpenAIRE |
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