Abstract: SA-PO0738
Tubular Galectin-3 Expression Is Associated with Worse Kidney Disease in Lupus Nephritis
Session Information
- Glomerular Diseases: Profiling Through Multiomics
November 08, 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
- Budhwani, Ayesha, University of Houston, Houston, Texas, United States
- Louis Sam Titus, Anto Sam Crosslee, University of Houston, Houston, Texas, United States
- Srinivasan, Vishal Akash A, University of Houston, Houston, Texas, United States
- Sherwani, Ali, University of Houston, Houston, Texas, United States
- Appalaneni, Rohith, University of Houston, Houston, Texas, United States
- Chen, Shu-Hsia, Houston Methodist Hospital, Houston, Texas, United States
- Saxena, Ramesh, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Cai, Qi, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Truong, Luan D., Houston Methodist Hospital, Houston, Texas, United States
- Wu, Tianfu, University of Houston, Houston, Texas, United States
- Mohan, Chandra, University of Houston, Houston, Texas, United States
Background
Galectin-3 (Gal-3) is reported to be increased in Lupus Nephritis (LN) serum, associated with worse disease. Here, we explore the intra-renal origins of Gal-3 using spatial proteomics.
Methods
LN and transplant control kidneys (N=12) were subjected to 18-plex spatial proteomics using multiplexed immunofluorescence staining. An independent cohort of 12 LN renal biopsies was used for Visium spatial transcriptomics. QuPath and MATLAB were used for quantification.
Results
LN renal biopsies exhibited significantly higher Gal-3 (8.2-fold, p<0.01) compared to controls. LN biopsies exhibited 7.9-fold Gal-3 increase in tubules (p<0.01), 12.6-fold increase in podocytes (p<0.01), 4.5-fold increase in endothelial cells (p<0.05), 32.2-fold increase in smooth muscle actin (SMA+) cells (p<0.01), and 97-fold increase in immune cells (p<0.01). Among the renal tubules, Gal-3 expression was highest in Distal Convoluted Tubules, marked by higher E-cad expression (Fig. 1). Spatial transcriptomics of 12 independent LN biopsies revealed upregulated Gal-3 in regions affected by tubular atrophy, interstitial inflammation, and immune hotspots (p<0.05 for all). In vitro, LN urine and TGF-β significantly increased Gal-3 protein levels in renal tubular cells (2.3-fold and 1.4-fold, respectively). Public datasets corroborated the elevated Gal-3 mRNA in LN glomeruli, compared to healthy controls.
Conclusion
Our findings indicate that the increased Galectin-3 in LN tubules and immune cells is closely linked to inflammatory and fibrotic disease progression in LN. Mechanistic studies are warranted to dissect out the role of Gal-3 in LN, and to test its suitability as a therapeutic target.
Figure 1. Galectin-3 expression within renal tubule clusters. The images are representative of tubule ROI from 6 control and 6 LN renal biopsies. Pseudo-colors are used for different segments of tubules; B-cat, E-cad, Aqp-3, and Pan-Ck, along with Gal-3