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Further Evidence That the Soluble Urokinase Plasminogen Activator Receptor Does Not Directly Injure Mice or Human Podocytes.
Harel, Efrat; Shoji, Jun; Abraham, Vivek; Miller, Loan; Laszik, Zoltan G; King, Andrew; Dobi, Dejan; Szabo, Gyula; Hann, Byron; Sarwal, Minnie M; Craik, Charles S; Vincenti, Flavio.
Afiliación
  • Harel E; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA.
  • Shoji J; Kidney Transplant Service, University of California, San Francisco, CA.
  • Abraham V; AbbVie, Renal Discovery, Chicago, IL.
  • Miller L; AbbVie, Renal Discovery, Chicago, IL.
  • Laszik ZG; Kidney Transplant Service, University of California, San Francisco, CA.
  • King A; AbbVie, Renal Discovery, Chicago, IL.
  • Dobi D; Kidney Transplant Service, University of California, San Francisco, CA.
  • Szabo G; Kidney Transplant Service, University of California, San Francisco, CA.
  • Hann B; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA.
  • Sarwal MM; Division of Transplant Surgery, University of California San Francisco, San Francisco, CA.
  • Craik CS; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA.
  • Vincenti F; Kidney Transplant Service, University of California, San Francisco, CA.
Transplantation ; 104(1): 54-60, 2020 01.
Article en En | MEDLINE | ID: mdl-31449183
BACKGROUND: The role of the soluble urokinase plasminogen activator receptor (suPAR) in focal segmental glomerulosclerosis (FSGS) as the circulating factor or as a predictor of recurrence after transplantation remains controversial. Previously published studies in mice and isolated podocytes produced conflicting results on the effect of suPAR on podocyte injury, effacement of foot processes, and proteinuria. These discordant results were in part due to diverse experimental designs and different strains of mice. The aim of our study was to determine the reasons for the inconsistencies of the previous studies results with suPAR by using uniform methods and studies in different strains of mice. METHODS: We utilized a primary culture of human podocytes and 2 mouse models, the wild type (WT) and the urokinase plasminogen activator receptor (uPAR) KO (uPAR), in an attempt to resolve the reported conflicting results. RESULTS: In both WT and uPAR mouse models, injection of recombinant uPAR, even at a high dose (100 µg), did not induce proteinuria, effacement of podocytes, or disruption of the cytoskeleton. Injection of suPAR resulted in its deposition exclusively in the glomerular endothelial cells and not in the podocytes of WT mice and was not detected at the uPAR KO mice. Kidneys from patients with recurrent FSGS had negative immunostaining for uPAR. We also evaluated the effect of recombinant uPAR on primary culture of human podocytes. uPAR did not result in podocytes damage. CONCLUSIONS: suPAR by itself is not the cause for direct podocyte injury, in vitro or in vivo. These findings suggest a more complex and still poorly understood role of suPAR in FSGS.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glomeruloesclerosis Focal y Segmentaria / Podocitos / Receptores del Activador de Plasminógeno Tipo Uroquinasa Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Transplantation Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glomeruloesclerosis Focal y Segmentaria / Podocitos / Receptores del Activador de Plasminógeno Tipo Uroquinasa Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Transplantation Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos