Glycosphingolipids as Therapeutic Targets and Biomarkers of Lupus Nephritis
Abstract
The oseltamivir phosphate (OP) treatment of the MRL/lpr lupus prone strain has been completed for half of the mice and most samples analyzed, including proteinuria, renal pathology, circulating activated T cell numbers, kidney glycosphingolipid levels, and spleen weight and length. Treatment of the remaining half of the MRL/lpr mice was just completed and sample analysis will begin immediately. The B6.SLE1/2/3 genetic study (Neu1+/+ vs Neu1+/- mice) is underway and nearing completion. For the exosome biomarker study, exosomes have been isolated from most of the urine samples and proteomic and lipid discovery analyses run on a subset of samples. Proteomics analysis of this subset identified several proteins previously reported/validated as urine biomarkers of lupus nephritis. Additionally, several proteins were detected predominantly in treatment responders compared to non-responders or predominantly in non-responders compared to responders, which may be useful as biomarkers of response to therapy. These results are being confirmed in the remaining samples. In addition, we are investigating the role of NEU1 in the function of renal mesangial cells using cells isolated from the Neu1+/+ and Neu1+/- mice and have demonstrated that NEU mediates cytokine release in part through a TLR4-MAPK p38 pathway in cells stimulated with lupus serum.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2018
- Accession Number
- AD1094202
Entities
People
- Bethany Wolf
- James Oates
- Jessalyn Rodgers
- Kamala Sundararaj
- Michael G. Janech
- Richard Drake
- Tamara K Nowling
Organizations
- Medical University of South Carolina