Abstract: TH-PO0295
HSP27 Promotes Activation of Parietal Epithelial Cells and Crescent Formation in Crescentic Glomerulonephritis
Session Information
- Glomerular Diseases: Cell Biology
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Melis, Lisa, Sorbonne Universite, Paris, France
- Sakhi, Hamza, Assistance Publique - Hopitaux de Paris, Créteil, Île-de-France, France
- Audard, Vincent, Assistance Publique - Hopitaux de Paris, Créteil, Île-de-France, France
- Gallazzini, Morgan, Centre de Recherche sur l'Inflammation, Paris, Île-de-France, France
- El Karoui, Khalil, Assistance Publique - Hopitaux de Paris, Créteil, France
Group or Team Name
- Common and Rare Kidney Disease
Background
Crescentic glomerulonephritis (CrGN) is the most severe form of glomerular disease and leads to end stage renal disease in 30-50% of cases. It is characterized by the pathological accumulation of parietal epithelial cells (PEC) forming cellular crescents in the urinary space. Current treatments rely on immunosuppressive therapies and do not directly target molecular pathways driving crescent formation and PEC activation. Heat Shock Protein 27 (HSP27) is a stress-induced chaperone protein with anti-apoptotic and pro-proliferative properties. Here, we investigated the role of HSP27 in PEC activation and crescent formation.
Methods
To investigate the role of HSP27, we employed both genetic and pharmacological approaches. Mice with PEC-specific deletion of HSP27 (iPEC-Cre::Hspb1 fl/fl) or treated with the HSP27 inhibitor OGX-427 were subjected to nephrotoxic serum (NTS)–induced CrGN preclinical model. Kidney biopsies from patients with CrGN (N=13) were analyzed. In vitro, primary PEC cultures were exposed to HB-EGF, with or without HSP27 knockdown or OGX-427 treatment, to assess cell migration, proliferation, and activation markers (including CD44, Cld-1, CD9, and EGFR activation).
Results
HSP27 was strongly overexpressed in PEC within glomerular crescents in both human CrGN biopsies and NTS-treated mice. Moreover, serum HSP27 levels were significantly increased in patients. PEC-specific deletion of HSP27 delayed disease progression and significantly reduced crescent formation, associated with decreased expression CD44, Cld-1 and CD9. Importantly, iPEC-CRE::Hspb1 fl/fl mice displayed preserved renal function and reduced albuminuria compared with control mice. We then assessed whether pharmacological inhibition of HSP27 could similarly mitigate crescent formation and PEC activation. Indeed, targeting HSP27 with OGX in mice reduced crescent formation and decreased PEC activation markers expression. In vitro, pharmacologic or genetic silencing of HSP27 in PEC significantly reduced PEC migration and activation. Mechanistically, HSP27 knockdown led to decreased EGFR activation, suggesting that HSP27 promotes PEC activation and crescent formation at least partly through the EGFR signaling pathway.
Conclusion
Taken together, our data highlight a role for HSP27 in the development of crescent lesions and pave the way for innovative therapeutic approaches for CrGN patients.
Funding
- Government Support – Non-U.S.