Dendrin Ablation Prolongs Life Span by Delaying Kidney Failure
Autor: | Monica Schwartzman, Karl Tryggvason, Lisette Casagrande, John M. Basgen, Kristin Meliambro, Astrid Weins, Jaakko Patrakka, Peter Mundel, Susanne B. Nicholas, Ilse Daehn, R K Gupta, Andrey S. Shaw, Kirk N. Campbell, David Lessman, John Cijiang He, Jenny Wong |
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Rok vydání: | 2015 |
Předmět: |
Kidney
medicine.medical_specialty Proteinuria biology business.industry Dendrin medicine.medical_treatment Urology medicine.disease Ablation Pathology and Forensic Medicine Podocyte medicine.anatomical_structure Endocrinology Internal medicine medicine biology.protein Renal replacement therapy medicine.symptom business Dialysis Kidney disease |
Zdroj: | The American Journal of Pathology. 185:2143-2157 |
ISSN: | 0002-9440 |
Popis: | Podocyte loss is central to the progression of proteinuric kidney diseases leading to end-stage kidney disease (ESKD), requiring renal replacement therapy, such as dialysis. Despite modern tools and techniques, the 5-year mortality of some patients requiring dialysis remains at about 70% to 80%. Thus, there is a great unmet need for podocyte-specific treatments aimed at preventing podocyte loss and the ensuing development of ESKD. Here, we show that ablation of the podocyte death-promoting protein dendrin delays the onset of ESKD, thereby expanding the life span of mice lacking the adapter protein CD2AP. Ablation of dendrin delays onset and severity of proteinuria and podocyte loss. In addition, dendrin ablation ameliorates mesangial volume expansion and up-regulation of mesangial fibronectin expression, which is mediated by a podocyte-secreted factor. In conclusion, onset of ESKD and death can be markedly delayed by blocking the function of dendrin. |
Databáze: | OpenAIRE |
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