Kidney Week

Abstract: TH-PO0264

Suppression of Endothelial Ephrin-B2 Improves Albuminuria in FSGS

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

• Miyake, Hiromasa, Okayama Daigaku, Okayama, Okayama Prefecture, Japan

Hiromasa Miyake, MD, PhD

• Nakayama, Masanori, Okayama Daigaku, Okayama, Okayama Prefecture, Japan

Masanori Nakayama, DrPH

• Hikita, Takao, Okayama Daigaku, Okayama, Okayama Prefecture, Japan

Takao Hikita, PhD

• Campbell, Kirk N., University of Pennsylvania, Philadelphia, Pennsylvania, United States

Kirk N. Campbell, MD, FASN

Background

Glomerular diseases are mainly characterized by podocyte injury. Although podocytes play a central role in maintaining filtration integrity, therapies that directly target podocytes have not yet been established. While circulating factors have been reported to mediate some podocytopathies including primary focal segmental glomerulosclerosis (FSGS), none has been shown to play a causal role. Ephrin-B2, a transmembrane ligand of EphB receptor tyrosine, is predominantly expressed in endothelial cells and plays a pivotal role during angiogenesis. Ephrin-B2 can interact EphB4 on podocytes, but the role of this signal pathway remains unclear.

Methods

We analyzed kidneys from endothelial cell-specific inducible ephrin-B2 knockout (Efnb2^iΔEC) mice and podocyte-specific inducible EphB4 knockout (EphB4^iΔPod) mice. To investigate functional link between ephrin-B2/EphB4 forward signaling and podocyte integrity, immunoprecipitation of EphB4 from kidney tissues was examined. Given that ephrin-B2 is secreted by endothelial cells, we then measured serum ephrin-B2 levels in FSGS patients and kidney transplantation donors.

Results

In Efnb2^iΔEC mice, nephrin, one of the most important slit diaphragm proteins, was upregulated in the kidneys. Similar results were observed in EphB4^iΔPod mice and nephrin was co-immunoprecipitated with EphB4, suggesting that ephrin-B2/EphB4 forward signaling is involved in the regulation of nephrin expression. Serum ephrin-B2 levels were elevated in FSGS patients compared with donors.

Conclusion

Loss of endothelial ephrin-B2 function contributes to the maintenance of podocyte integrity through upregulation of nephrin expression. Moreover, secreted ephrin-B2 may serve as a causative circulating mediator in FSGS.

Acknowledgment

The present study was supported by Grants-in-Aid for Scientific Research-Fund for the promotion of Joint International Research (Fostering Joint International Research (B)), by JST Commercialization Support, Grant Number, JPMJSF2325, Japan, by AMED under Grant Number JP256f0137010.

A-B) Analysis of kidneys from Efnb2^iΔEC mice. Nephrin immunostaining images (A) and signal quantification data (B) are shown. C-D) Analysis of kidneys from EphB4^iΔPod mice. Nephrin immunostaining images (C) and signal quantification data (D) are shown.

Funding

• Government Support – Non-U.S.