Full-length soluble urokinase plasminogen activator receptor down-modulates nephrin expression in podocytes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-11

AUTHORS

Massimo Alfano, Paola Cinque, Guido Giusti, Silvia Proietti, Manuela Nebuloni, Silvio Danese, Silvia D’Alessio, Marco Genua, Federica Portale, Manuela Lo Porto, Pravin C. Singhal, Maria Pia Rastaldi, Moin A. Saleem, Domenico Mavilio, Joanna Mikulak

ABSTRACT

Increased plasma level of soluble urokinase-type plasminogen activator receptor (suPAR) was associated recently with focal segmental glomerulosclerosis (FSGS). In addition, different clinical studies observed increased concentration of suPAR in various glomerular diseases and in other human pathologies with nephrotic syndromes such as HIV and Hantavirus infection, diabetes and cardiovascular disorders. Here, we show that suPAR induces nephrin down-modulation in human podocytes. This phenomenon is mediated only by full-length suPAR, is time-and dose-dependent and is associated with the suppression of Wilms' tumor 1 (WT-1) transcription factor expression. Moreover, an antagonist of αvβ3 integrin RGDfv blocked suPAR-induced suppression of nephrin. These in vitro data were confirmed in an in vivo uPAR knock out Plaur(-/-) mice model by demonstrating that the infusion of suPAR inhibits expression of nephrin and WT-1 in podocytes and induces proteinuria. This study unveiled that interaction of full-length suPAR with αvβ3 integrin expressed on podocytes results in down-modulation of nephrin that may affect kidney functionality in different human pathologies characterized by increased concentration of suPAR. More... »

PAGES

13647

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep13647

DOI

http://dx.doi.org/10.1038/srep13647

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1036013375

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26380915


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