Abstract: TH-PO0680
Role of sCD89 Myeloid Receptor in Glomerular Hypercellularity in Childhood IgAN
Session Information
- Glomerular Diseases: Immunopathogenesis and Targeted Therapeutics
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Badie, Amandine, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Lachize Neanne, Lison, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Sahu, Srishti, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Leenhardt, Diane, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Mathieu, Hélène, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Bonnefoy, Arnaud, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Alexandra, Cambier, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
Group or Team Name
- Cambier Laboratory.
Background
Childhood immunoglobulin A nephropathy (cIgAN) is one of the most common primary glomerulonephritis. It manifests as recurrent hematuria and proteinuria, associated with renal inflammation and glomerular mesangial hypercellularity. Without early diagnosis and targeted treatment, up to 40% of patients may progress to end-stage renal disease within 20 years. This autoimmune disease is characterized by glomerular deposition of circulating immune complexes (CICs). Soluble CD89 (sCD89), present in CICs, plays a key role in inflammation and mesangial proliferation in cIgAN through the involvement of the transferrin receptor 1 (TfR1) and activation of the PI3K/mTOR pathway. However, the underlying molecular mechanisms remain poorly understood. In this study, we investigate the mechanisms by which sCD89 regulates TfR1, and the requirement of TfR1 in mediating sCD89-induced activation of the PI3K/Akt/mTOR signaling pathway in human mesangial cells (HMCs).
Methods
HMCs were stimulated with recombinant sCD89 (rsCD89) and the expression of TfR1 was analyzed by RT-qPCR, western blot, immunofluorescence, and flow cytometry. In parallel, cells were treated with siRNA targeting TfR1, and the protein expression and phosphorylation of key components of the PI3K/Akt/mTOR pathway, including p70S6K1, 4E-BP1, and S6Rp, were analyzed by western blot.
Results
TfR1 was found to be consistently expressed in HMCs and was upregulated at both mRNA and protein levels 24 hours after rsCD89 stimulation. HMC stimulation with rsCD89 also increased the expression and phosphorylation of Akt (p-T308, p-S473), mTOR (p-S2448), and p70S6K1 (p-T389), while their levels were markedly decreased when TfR1 was silenced.
Conclusion
These findings strongly support the involvement of sCD89 in mesangial cell proliferation through its regulation on TfR1 expression and mTOR pathway activation. This study significantly advances our understanding of the the functional connections between sCD89, TfR1, and mTOR signaling, offering a promising foundation for new therapeutic approaches targeting mesangial hypercellularity and inflammation in cIgAN.