Abstract: FR-PO841
EPHB2 Mediates Inflammation in Podocytes of Lupus Nephritis
Session Information
- Glomerular Diseases: Inflammation and Immunology
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Peng, Huajing, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Luo, Zilv, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Chen, Wei, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
Background
Podocyte injury in lupus nephritis (LN) is a critical contributor to the substantial proteinuria observed in LN patients. However, the potential for a unique inflammatory pattern of podocyte injury specific to lupus nephritis remains to be elucidated. The erythropoietin-producing hepatocellular receptor (Eph) family, the largest group of receptor tyrosine kinases, have been implicated in a wide range of diseases. Elevated expression of EPHB2 has been observed in the kidneys of models with IgA nephropathy (IgAN) and ischemia-reperfusion (IR) injury. However, the specific role of EPHB2 in the context of podocyte injury in lupus nephritis remains unknown.
Methods
To investigate the underlying mechanisms, we developed a nephrotoxic nephritis (NTN) mouse model of lupus and an IFNα-stimulated podocyte injury model.We observed changes in proteinuria and renal pathology in the mice. The expression of inflammatory proteins like MMP7,VCAM-1 and the activity of the NFκB pathway were assessed using Western blotting, and immunofluorescence. Additionally, we utilized adenoviral vectors to interference with EPHB2 expression in vivo and in vitro.Similar methods were employed to detect and compare the expression of inflammatory molecules before and after EPHB2 interference.
Results
In vivo experiments revealed that NTN lupus mice exhibited significantly increased proteinuria and severe glomerulosclerosis. In vitro, IFNα stimulation led to cytoskeletal protein disruption in podocytes. Elevated expression of MMP7 and VCAM1, as well as increased activity of the NFκB pathway, were observed in the renal cortex of NTN lupus mice and in IFNα-stimulated podocytes. Interference with EPHB2 expression in the kidney resulted in a significant reduction in proteinuria and alleviation of glomerulosclerosis in NTN lupus mice. Additionally, the expression of MMP7 and VCAM1, as well as the activity of the NFκB pathway, were significantly reduced in both the renal cortex and IFNα-stimulated podocytes after EPHB2 expression was inhibited.
Conclusion
High expression of EPHB2 in podocytes is implicated in the activation of renal inflammation in LN. Interfering with EPHB2 expression in vivo and in vitro have been shown to alleviation podocyte inflammation and improve renal outcomes by inhibiting the NFκB pathway. Intervention targeting EPHB2 represents an effective strategy for controlling inflammation activation in LN podocytes.