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' 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

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' 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

Investigating hydrological regimes and processes in a set of catchments with temporary waters in Mediterranean Europe

Seven catchments of diverse size in Mediterranean Europe were investigated in order to understand the main aspects of their hydrological functioning. The methods included the analysis of daily and monthly precipitation, monthly potential evapotranspiration rates, flow duration curves, rainfall runoff relationships and catchment internal data for the smaller and more instrumented catchments. The results showed that the catchments were less dry than initially considered. Only one of them was really semi-arid throughout the year. All the remaining catchments showed wet seasons when precipitation exceeded potential evapotrans-piration, allowing aquifer recharge, wet runoff generation mechanisms and relevant baseflow contribution. Nevertheless, local infiltration excess (Hortonian) overland flow was inferred during summer storms in some catchments and urban overland flow in some others. The roles of karstic groundwater, human disturbance and low winter temperatures were identified as having an important impact on the hydrological regime in some of the catchments