Author:
Niasse Aïssata,Louis Kevin,Lenoir Olivia,Schwarz Chloé,Xu Xiaoli,Couturier Aymeric,Dobosziewicz Hélène,Corchia Anthony,Placier Sandrine,Vandermeersch Sophie,Hennighausen Lothar,Frere Perrine,Galichon Pierre,Surin Brigitte,Ouchelouche Souhila,Louedec Liliane,Migeon Tiffany,Verpont Marie-Christine,Buob David,Xu-Dubois Yi-Chun,Francois Hélène,Rondeau Eric,Mesnard Laurent,Hadchouel Juliette,Luque Yosu
Abstract
AbstractDuring glomerular diseases, podocyte-specific pathways can modulate the intensity of the lesions and prognosis. The therapeutic targeting of these pathways could thus improve the management and prognosis of chronic kidney diseases. The Janus Kinase/ Signal Transducer and Activator of Transcription (JAK/STAT) pathway, classically described in immune cells, has been recently described in intrinsic kidney cells. Here, we show, for the first time, that STAT5 is activated in human podocytes in focal segmental glomerulosclerosis (FSGS). Additionally,Stat5podocyte-specific inactivation aggravates the functional and structural alterations in a mouse model of FSGS. This could be due, at least in part, to an inhibition of the autophagic flux. Finally, Interleukin 15 (IL-15), a classical activator of STAT5 in immune cells, increases STAT5 phosphorylation in human podocytes and its administration alleviates glomerular injuryin vivoby maintaining the autophagy flux in podocytes. In conclusion, activating podocytic STAT5 with commercially available IL-15 represents a new therapeutic avenue with the potential for FSGS.
Publisher
Cold Spring Harbor Laboratory