Downregulation of megalin, cubilin, ClC-5 and podocin in Fabry nephropathy: potential implications in the decreased effectiveness of enzyme replacement therapy
| Autor: | Dorella Del Prete, Lisa Gianesello, Alejandro Iotti, Monica Ceol, Giovanna Priante, Hernán Trimarchi |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Nephrology medicine.medical_specialty 030232 urology & nephrology Podocyte Down-Regulation Receptors Cell Surface 030204 cardiovascular system & hematology urologic and male genital diseases Nephropathy 03 medical and health sciences Megalin 0302 clinical medicine Chloride Channels Chronic kidney disease Internal medicine Podocin Humans Medicine Enzyme Replacement Therapy biology urogenital system business.industry End-stage kidney disease Intracellular Signaling Peptides and Proteins Membrane Proteins Enzyme replacement therapy Middle Aged medicine.disease Cubilin Fabry disease Proteinuria Low Density Lipoprotein Receptor-Related Protein-2 Endocrinology medicine.anatomical_structure biology.protein CLC-5 Fabry Disease Female business Synaptopodin Kidney disease |
| Zdroj: | Journal of Nephrology. 34:1307-1314 |
| ISSN: | 1724-6059 1121-8428 |
| Popis: | Fabry disease is an X-linked disorder due to mutations in α-galactosidase A, resulting in the accumulation of enzyme substrates and cell malfunction. Kidney involvement is frequent, affecting all native kidney cell types. Podocyte damage results in proteinuria and chronic kidney disease. End-stage kidney disease is the rule in middle-aged males and some females with the classic phenotype. In podocytes and kidney proximal tubular cells, megalin is one of the molecules involved in enzyme replacement therapy (ERT) cellular absorption. After podocyte damage, podocin concentration is decreased and contributes to progressive proteinuria. We report in a male and a female patient the decreased expression of megalin, cubilin, ClC-5 and podocin compared to controls and chronic kidney disease (CKD) biopsies. Moreover, the decrease in ClC-5, a molecule engaged in endosomal-lysosomal acidification, could also affect ERT. These findings may partially explain some of the dysfunctions described in Fabry nephropathy and could highlight possible alterations in the pharmacokinetics of the delivered enzyme. |
| Databáze: | OpenAIRE |
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