Administration of recombinant soluble urokinase receptor per se is not sufficient to induce podocyte alterations and proteinuria in mice.
Circulating levels of soluble forms of urokinase-type plasminogen activator receptor (suPAR) are generally elevated in sera from children and adults with FSGS compared with levels in healthy persons or those with other types of kidney disease. In mice lacking the gene encoding uPAR, forced increases in suPAR concentration result in FSGS-like glomerular lesions and proteinuria. However, whether overexpression of suPAR, per se, contributes to the pathogenesis of FSGS in humans remains controversial. We conducted an independent set of animal experiments in which two different and well characterized forms of recombinant suPAR produced by eukaryotic cells were administered over the short or long term to wild-type (WT) mice. In accordance with the previous study, the delivered suPARs are deposited in the glomeruli. However, such deposition of either form of suPAR in the kidney did not result in increased glomerular proteinuria or altered podocyte architecture. Our findings suggest that glomerular deposits of suPAR caused by elevated plasma levels are not sufficient to engender albuminuria.
Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155 - "Rare and common kidney diseases, matrix remodeling and tissue repair," Paris, France; Institut National de la Santé et de la Recherche Médicale UMR_S 1155 - "Rare and common kidney diseases, matrix remodelling and tissue repair," and.
Dominique
D
Cathelin
Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155 - "Rare and common kidney diseases, matrix remodeling and tissue repair," Paris, France; Institut National de la Santé et de la Recherche Médicale UMR_S 1155 - "Rare and common kidney diseases, matrix remodelling and tissue repair," and.
Sandrine
S
Placier
Finsen Laboratory and Bric, Rigshospitalet, Copenhagen, Denmark.
Michael
M
Ploug
Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155 - "Rare and common kidney diseases, matrix remodeling and tissue repair," Paris, France; Institut National de la Santé et de la Recherche Médicale UMR_S 1155 - "Rare and common kidney diseases, matrix remodelling and tissue repair," and.
Marie-Christine
MC
Verpont
Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155 - "Rare and common kidney diseases, matrix remodeling and tissue repair," Paris, France; Institut National de la Santé et de la Recherche Médicale UMR_S 1155 - "Rare and common kidney diseases, matrix remodelling and tissue repair," and.
Sophie
S
Vandermeersch
Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155 - "Rare and common kidney diseases, matrix remodeling and tissue repair," Paris, France; Institut National de la Santé et de la Recherche Médicale UMR_S 1155 - "Rare and common kidney diseases, matrix remodelling and tissue repair," and Assistance Publique-Hôpitaux de Paris, Nephrological Emergencies and Renal Transplantation, Tenon Hospital, Paris, France; and.
Yosu
Y
Luque
Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155 - "Rare and common kidney diseases, matrix remodeling and tissue repair," Paris, France; Institut National de la Santé et de la Recherche Médicale UMR_S 1155 - "Rare and common kidney diseases, matrix remodelling and tissue repair," and Assistance Publique-Hôpitaux de Paris, Nephrological Emergencies and Renal Transplantation, Tenon Hospital, Paris, France; and.
Alexandre
A
Hertig
Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155 - "Rare and common kidney diseases, matrix remodeling and tissue repair," Paris, France; Institut National de la Santé et de la Recherche Médicale UMR_S 1155 - "Rare and common kidney diseases, matrix remodelling and tissue repair," and Assistance Publique-Hôpitaux de Paris, Nephrological Emergencies and Renal Transplantation, Tenon Hospital, Paris, France; and.
Eric
E
Rondeau
Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155 - "Rare and common kidney diseases, matrix remodeling and tissue repair," Paris, France; Institut National de la Santé et de la Recherche Médicale UMR_S 1155 - "Rare and common kidney diseases, matrix remodelling and tissue repair," and Assistance Publique-Hôpitaux de Paris, Nephrological Emergencies and Renal Transplantation, Tenon Hospital, Paris, France; and laurent.mesnard@tnn.aphp.fr.
Laurent
L
Mesnard
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008810:Mice, Inbred C57BL; D009393:Nephritis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology*; D011507:Proteinuria / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D055293:Receptors, Urokinase Plasminogen Activator / Q000008:administration & dosage / Q000502:physiology*; D011994:Recombinant Proteins / Q000008:administration & dosage
D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins
glomerulosclerosis; nephrotic syndrome; pathophysiology of renal disease and progression; podocyte; proteinuria