Abstract: TH-PO0411
Ganglioside GM3 Attenuates Podocyte Injury in Lupus Nephritis via Suppression of Endoplasmic Reticulum (ER) Stress and Apoptosis
Session Information
- Glomerular Diseases: Autoimmune Diseases
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
- Mo, Xilong, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guo, Jing, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Xin, Yangyang, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Yang, Xiao, 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 is a central driver of proteinuria in lupus nephritis (LN). Ganglioside GM3 is a cell membrane-resident sialylated glycosphingolipid that plays key roles in cell morphology, adhesion, signal transduction, and immune regulation. Dysregulated glycosphingolipid metabolism has been implicated in LN; however, the role of ganglioside GM3 in podocyte injury remains unclear. We investigated the clinical relevance, functional role, and underlying mechanisms of GM3 in LN.
Methods
Plasma GM3 levels were measured in LN patients and healthy controls and correlated with disease activity and proteinuria. GM3 levels and metabolic enzyme expression were assessed in three LN mouse models (cGVHD, NTS, and MRL/lpr). Exogenous GM3 was administered to LN mice to evaluate its effects on renal pathology, immune complex deposition, and proteinuria. Localization of GM3 in glomeruli was examined by immunofluorescence. In vitro, human podocytes (HPC) were stimulated with IFN-α to mimic the lupus microenvironment, followed by GM3 supplementation and RNA sequencing to explore mechanisms.
Results
GM3 levels were significantly reduced in LN patients and inversely correlated with disease activity and proteinuria. Consistent reductions were observed in plasma and kidneys of LN mice, correlating with renal injury severity. Increased expression of GM3-metabolizing enzymes (NEU3 and B4GALNT1) was associated with decreased GM3 levels. GM3 administration markedly ameliorated glomerular injury, reduced immune complex deposition, and decreased proteinuria in LN mice. GM3 localized predominantly to podocytes and was reduced in diseased glomeruli. In vitro, IFN-α induced GM3 depletion and podocyte injury, whereas GM3 supplementation restored podocyte integrity. Transcriptomic analysis revealed that GM3 reversed IFN-α–induced endoplasmic reticulum stress and apoptosis pathways.
Conclusion
GM3 deficiency is a conserved feature of LN and correlates with disease severity. Restoring GM3 alleviates podocyte injury and improves renal outcomes, likely by suppressing ER stress and apoptosis. These findings identify GM3 dysregulation as a novel pathogenic mechanism and highlight GM3 as a potential therapeutic target in LN.