Abstract: SA-PO0737
Subset of Dysregulated Pathways in Lupus Nephritis Renal Tubules May Be Driven by Serum-Derived Factors
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 Cullen College of Engineering, Houston, Texas, United States
- Louis Sam Titus, Anto Sam Crosslee, University of Houston Cullen College of Engineering, Houston, Texas, United States
- Maruvada, Vinaika, University of Houston Cullen College of Engineering, Houston, Texas, United States
- Shaik, Wasim Akram, University of Houston, Houston, Texas, United States
- Nguyen, Lana C., University of Houston, Houston, Texas, United States
- Mohan, Chandra, University of Houston Cullen College of Engineering, Houston, Texas, United States
Background
How systemic factors in Lupus Nephritis (LN) contribute to tubular injury is poorly understood. We explore this question by integrating in vitro transcriptomic data with spatial transcriptomics from LN renal biopsies to identify disease-relevant pathways.
Methods
Visium spatial transcriptomics was carried out in 12 LN renal biopsies with varying activity index (AI) and chronicity index (CI). In parallel, proximal tubule epithelial cells (PTECs; HK-2) were treated with 12 LN sera (or healthy control (HC) sera), followed by bulk RNA sequencing. The overlap between these two transcriptomic datasets was deduced.
Results
Out of 543 differentially expressed genes in PTEC (LN sera vs HC sera), 40 were upregulated and 110 were downregulated at a Fold Change threshold of 2 and p<0.5. Among the genes triggered in PTECs by lupus sera, several correlated positively (n=17) or negatively (n=16) with renal pathology AI (p<0.05), or positively (n=2) or negatively (n=6) with CI (p<0.05), based on spatial transcriptomic analysis. Notable examples include ATP6V1B1, a gene implicated in renal tubular acidosis, SLC34A3, a gene linked to renal phosphate wasting, and GLUD1, a gene linked to renal fibrosis, in the literature.
Conclusion
This study demonstrates that a subset of the transcriptional signatures in PTEC cells in LN may be the consequence of exposure to serum derived factors. Studies are underway to elucidate these systemic triggers of renal injury in LN.
Figure 1. LN serum Upregulated or Downregulated multiple genes in PTEC cells, compared to healthy serum.