{Reference Type}: Journal Article
{Title}: Protective Role of the Podocyte IL-15 / STAT5 Pathway in Focal Segmental Glomerulosclerosis.
{Author}: Niasse A;Louis K;Lenoir O;Schwarz C;Xu X;Couturier A;Dobosziewicz H;Corchia A;Placier S;Vandermeersch S;Hennighausen L;Frère P;Galichon P;Surin B;Ouchelouche S;Louedec L;Migeon T;Verpont MC;Yousfi N;Buob D;Xu-Dubois YC;François H;Rondeau E;Mesnard L;Hadchouel J;Luque Y;
{Journal}: Kidney Int Rep
{Volume}: 9
{Issue}: 4
{Year}: 2024 Apr
{Factor}: 6.234
{DOI}: 10.1016/j.ekir.2024.01.010
{Abstract}: UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Activating podocyte STAT5 with commercially available IL-15 represents a potential new therapeutic avenue for FSGS.