%0 Journal Article
%T Protective Role of the Podocyte IL-15 / STAT5 Pathway in Focal Segmental Glomerulosclerosis.
%A Niasse A
%A Louis K
%A Lenoir O
%A Schwarz C
%A Xu X
%A Couturier A
%A Dobosziewicz H
%A Corchia A
%A Placier S
%A Vandermeersch S
%A Hennighausen L
%A Frère P
%A Galichon P
%A Surin B
%A Ouchelouche S
%A Louedec L
%A Migeon T
%A Verpont MC
%A Yousfi N
%A Buob D
%A Xu-Dubois YC
%A François H
%A Rondeau E
%A Mesnard L
%A Hadchouel J
%A Luque Y
%J Kidney Int Rep
%V 9
%N 4
%D 2024 Apr
%M 38765560
%F 6.234
%R 10.1016/j.ekir.2024.01.010
%X <B>UNASSIGNED: </B>During glomerular diseases, podocyte-specific pathways can modulate the intensity of histological disease and prognosis. The therapeutic targeting of these pathways could thus improve the management and prognosis of kidney diseases. The Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway, classically described in immune cells, has been recently described in detail in intrinsic kidney cells.<BR><B>UNASSIGNED: </B>We describe STAT5 expression in human kidney biopsies from patients with focal segmental glomerulosclerosis (FSGS) and studied mice with a podocyte-specific Stat5 deletion in experimental glomerular diseases.<BR><B>UNASSIGNED: </B>Here, we show, for the first time, that STAT5 is activated in human podocytes in FSGS. In addition, podocyte-specific Stat5 inactivation aggravates the structural and functional alterations in a mouse model of FSGS. This could be due, at least in part, to an inhibition of 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 injury in vivo by maintaining autophagic flux in podocytes.<BR><B>UNASSIGNED: </B>Activating podocyte STAT5 with commercially available IL-15 represents a potential new therapeutic avenue for FSGS.