Abstract: TH-PO0314
Soluble CD93 Mediates Podocyte Injury Through Activation of the TGF-β Pathway in Idiopathic Nephrotic Syndrome
Session Information
- Glomerular Diseases: Omics
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
- Islam, Md Imtiazul, Nationwide Children's Hospital, Columbus, Ohio, United States
- Nelson, Jonathan W., University of Southern California, Los Angeles, California, United States
- Fetsko, Audrey Rose, Nationwide Children's Hospital, Columbus, Ohio, United States
- Wang, Xin, Nationwide Children's Hospital, Columbus, Ohio, United States
- Cummins, Timothy, University of Louisville, Louisville, Kentucky, United States
- Daehn, Ilse S., Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Perin, Laura, Childrens Hospital Los Angeles, Los Angeles, California, United States
- Nargis, Nelofar, Nationwide Children's Hospital, Columbus, Ohio, United States
- Annesi, Lorenzo, University of Bologna, Bologna, Italy
- Johnson, Richard J., University of Colorado Denver, Denver, Colorado, United States
- Cara-Fuentes, Gabriel M., Nationwide Children's Hospital, Columbus, Ohio, United States
Background
Idiopathic nephrotic syndrome (INS) is considered autoimmune podocytopathy. However, endothelial- released soluble CD93(sCD93) has emerged as candidate mediator of podocyte injury via β1 integrin–FAK signaling, indicating a role of glomerular endothelial cells (GEnC). In INS patients, high urinary sCD93 is associated with loss of kidney function. In experimental models, CD93 blockade reduces proteinuria, podocyte loss, and glomerulosclerosis. These findings suggest a link between sCD93 and kidney disease progression, but the downstream pathways involved in podocyte injury remain unclear.
Methods
To gain mechanistic insights into CD93-mediated podocyte injury, we integrated transcriptomic (total RNA-seq) and phosphoproteomic profiling of cultured human podocytes exposed to recombinant CD93 (rCD93). Key targets were validated by western blotting, co-immunoprecipitation (co-IP), immunofluorescence (IF), and electric cell–substrate impedance sensing (ECIS) in vitro, as well as by immunohistochemistry (IHC) and spatial transcriptomics (Xenium In Situ Transcriptomics) in vivo.
Results
Among the top candidates identified by bulk RNA sequencing and phosphoproteomics, we focused on RANBP3, a regulator of the transforing growth factor beta (TGFβ) pathway. In cultured podocytes, sCD93 mediated TGFβ signaling, evidenced by elevated p-Smad2 and p-RANBP3, by binding to β1-integrin. In adriamycin (ADR)-treated mice, podocyte TGFβ was increased compared to control mice, and to ADR-mice receiving CD93 blockade. By spatial transcriptomic of kidney tissue from ADR mice, CD93 blockade mitigated TGFβ actiation in GEnEC and podocytes.
Conclusion
Soluble CD93 induces podocyte injury by activating the TGF-β pathway via β1 integrin–FAK signaling. CD93 blockade prevents glomerular endothelial cell (GEnC) and podocyte injury, highlighting a critical role for GEnC-podocyte crosstalk in INS and identifying CD93 as a potential therapeutic target.