Abstract: SA-PO074
Epithelial STAT5 Confers Protection Against Glomerular and Tubular Injury
Session Information
- AKI: Mechanisms - Primary Injury and Repair - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Niasse, Aïssata, Inserm UMR_S1155, Paris, France
- Louis, Kevin, Inserm UMR_S1155, Paris, France
- Couturier, Aymeric, Inserm UMR_S1155, Paris, France
- Vandermeersch, Sophie, Inserm UMR_S1155, Paris, France
- Sandrine, Placier, Inserm UMR_S1155, Paris, France
- Rondeau, Eric, Tenon Hospital. Assistance Publique Hôpitaux de Paris, Paris, France
- Mesnard, Laurent, Tenon Hospital. Assistance Publique Hôpitaux de Paris, Paris, France
- Luque, Yosu, Tenon Hospital. Assistance Publique Hôpitaux de Paris, Paris, France
Background
Recent data support Janus Kinase/signal transducers and activators of transcription (JAK/STAT) signaling, a pathway described in immune cells, as relevant to the kidney’s tissue-specific response to injury. Studies have shown a deleterious role of podocyte STAT3 in glomerular diseases and the involvement of tubular STAT3 in renal fibrosis. Recently, we showed a protective role for the podocyte gamma chain, a potential activator of STAT5, during experimental glomerulonephritis. Here, we hypothesized that STAT5 may protect the kidney epithelium.
Methods
Mice with a podocyte-specific deletion of STAT5 and their littermate controls were challenged with nephrotoxic serum or with adriamycin. Mice with an inducible tubular-specific deletion of STAT5 and their littermate controls were challenged with a cisplatin nephrotoxicity model. All mice were derived on a C57BL6/J genetic background.
We also investigated epithelial STAT5 activation by immunohistochemistry in different clinical nephropathies.
Results
Podocyte STAT5 deficiency exacerbated proteinuria in both nephrotoxic nephritis and adriamycin nephropathy. In addition, loss of STAT5 in podocytes associated with a loss of epithelial markers, such as nephrin, and exaggerated foot process effacement. Furthermore, podocytic STAT5 is activated in vitro by interleukin 15.
Tubular STAT5 deficiency aggravated renal dysfunction and tubular injury in cisplatin nephropathy.
In man, we observed STAT5 activation in injured podocytes in focal and segmental glomerulosclerosis, and in tubular cells in those with acute tubular injury.
Conclusion
Our results suggest a novel protective role of the STAT5 transcription factor in podocytes and tubular epithelium in experimental nephropathy. Our clinical data suggest a similar cellular activation of STAT5 as seen pre-clinically. Epithelial STAT5 activation could represent a potential therapeutic target in AKI.