Abstract: FR-PO805
Kidney NELL1 Expression Peaks during Onset of Autoimmunity in Genetically Predisposed SKG Mice
Session Information
- Glomerular Diseases: Inflammation and Immunology
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Kumasaka, Lisa T., Oregon Health & Science University School of Medicine, Portland, Oregon, United States
- Seufert, Amy L., Oregon Health & Science University, Portland, Oregon, United States
- Avasare, Rupali S., Oregon Health & Science University, Portland, Oregon, United States
- Vance, Emily E., Oregon Health & Science University, Portland, Oregon, United States
- Napier, Ruth J., Oregon Health & Science University, Portland, Oregon, United States
Background
Inflammation is a key process in disease, including autoimmune disorders and cancer. Neural Epidermal Growth Factor-Like 1 (NELL1) is a multifunctional protein involved in various cellular processes, including development and tissue repair. Understanding the relationship between inflammation and NELL1 expression can provide insights into inflammatory mechanisms underlying tissue-specific pathologies, including the autoimmune kidney disease, NELL1-Membranous Nephropathy (MN).
Methods
SKG mice were given one intraperitoneal injection of zymosan to induce T cell-mediated inflammation, followed by weekly clinical scoring for joint swelling, redness, or deformities (Rosenzweig et al., 2023). Mice were euthanized at 2, 4, and 8 weeks post-zymosan, kidneys and brains were harvested and stored in RNAlater. Tissues were homogenized, RNA isolated, and expression of Nell1 was measured via qRT-PCR.
Results
Inflammatory conditions due to zymosan induced autoimmune arthritis coincided with higher NELL1 expression levels in the kidney tissue of SKG mice compared to naïve SKG mice that did not receive the zymosan injection. NELL1 expression peaked at the 2-week post zymosan injection and showed a progressive decline at the 4-week and 8-week time points. While NELL1 expression does coincide with arthritic inflammation in this model, it is important to note that NELL1 does not peak when severity of autoimmune arthritis peaks.
Conclusion
Our research shows NELL1 mRNA expression is enhanced in zymosan induced autoimmune arthritic mice kidneys compared to naïve controls. Interestingly, NELL1 expression is elevated prior to peak arthritis. Our work provides foundational knowledge for the development of a mouse model to study mechanisms of kidney inflammation that drive the development of NELL1 MN.