Protective Role of Podocytic IL-15 / STAT5 Pathway in Experimental Focal and Segmental Glomerulosclerosis
Year: 2022
Type: preprint
Abstract: During 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, Stat5 podocyte-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 injury in vivo by 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.
Authors: Aïssata Niasse, Kevin Louis, Olivia Lenoir, Chloé Schwarz, Xiaoli Xu, Aymeric Couturier, Hélène Dobosziewicz, Anthony Corchia, Sandrine Placier, Sophie Vandermeersch, Lothar Hennighausen, Perrine Frere, Pierre Galichon, Brigitte Surin, Souhila Ouchelouche, Liliane Louedec, Tiffany Migeon, Marie-Christine Verpont, David Buob, Yi-Chun Xu-Dubois, Hélène Francois, Eric Rondeau, Laurent Mesnard, Juliette Hadchouel, Yosu Luque
Institutions: Inserm, Sorbonne Université, Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée, Université Paris Cité, Paris Cardiovascular Research Center, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Hôpital Tenon
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4308733441