ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: PO1716

Protective Role of the Epithelial STAT5 Pathway in Kidney Injury

Session Information

Category: Glomerular Diseases

  • 1204 Podocyte Biology

Authors

  • Niasse, Aïssata, INSERM, Paris, Île-de-France, France
  • Louis, Kevin, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France
  • Mesnard, Laurent, Sorbonne Universite, Paris, Île-de-France, France
  • Hadchouel, Juliette, INSERM, Paris, Île-de-France, France
  • Luque, Yosu, Sorbonne Universite, Paris, Île-de-France, France

Group or Team Name

  • Inserm UMR_S1155 team, Paris, France
Background

During kidney diseases, diverse tissue-specific pathways can regulate kidney injury and prognosis. Thus, therapeutic targeting of these pathways could 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.

Methods

We 1) analyzed STAT5 activation in kidney biopsies from patients with focal segmental glomerulosclerosis (FSGS) and acute tubular injury (ATI), 2) used experimental models of glomerular and tubular injury in mice with podocyte- or tubular-specific STAT5 deficiency, 3) studied transcriptomic modifications related to STAT5 deletion in human kidney epithelial cells, 4) explored interleukin-15 mediated STAT5 activation in podocytes and glomerular injury.

Results

Here, we show, for the first time, that STAT5 is activated in both human podocytes (Figure 1A) and tubular cells in FSGS and ATI, respectively. Additionally, STAT5 deficiency in either glomerular or tubular epithelium aggravates the functional and structural alterations in a range of experimental models of glomerular (Figure 1B) or tubular disease. STAT5 deficiency in kidney epithelial cells resulted in dysregulation of multiple metabolic pathways, including glycolysis and oxidative phosphorylation (Figure 1C). Interleukin 15 (IL-15), a classical activator of STAT5 in immune cells, increases STAT5 phosphorylation in human podocytes and alleviates glomerular injury in vivo (Figure 1D) by activating anti-apoptotic pathways.

Conclusion

In conclusion, activating renal epithelial STAT5 represents a new therapeutic avenue with the potential for a range of beneficial effects in kidney diseases.

A. STAT5B activation in human podocytes in FSGS. B. STAT5 podocyte deficiency aggravates adriamycin-induced proteinuria. C. CRISPR-Cas9 induced deletion of STAT5B from human kidney epithelial cells leads to disruption of metabolic pathways. D. IL-15 alleviates adriamycin-induced glomerular injury in mice