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

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\u27 tumor 1 (WT-1) transcription factor expression. Moreover, an antagonist of alpha v beta 3 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 alpha v beta 3 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

REM observations of GRB060418 and GRB060607A: the onset of the afterglow and the initial fireball Lorentz factor determination

Context. Gamma-ray burst (GRB) emission is believed to originate in highly relativistic fireballs. Aims. Currently, only lower limits were securely set to the initial fireball Lorentz factor Γο. We aim to provide a direct measure of Γο. Methods. The early-time afterglow light curve carries information about Γο, which determines the time of the afterglow peak. We have obtained early observations of the near-infrared afterglows of GRB 060418 and GRB 060607A with the REM robotic telescope. Results. For both events, the afterglow peak could be clearly singled out, allowing a firm determination of the fireball Lorentz of Γο ~400, fully confirming the highly relativistic nature of GRB fireballs. The deceleration radius was inferred to be R[dec] ≈ 10¹⁷ cm. This is much larger than the internal shocks radius (believed to power the prompt emission), thus providing further evidence for a different origin of the prompt and afterglow stages of the GRB