Glycosphingolipids as Therapeutic Targets and Biomarkers of Lupus Nephritis
Technical Report,30 Sep 2017,29 Sep 2018
Medical University of South Carolina Charleston United States
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The oseltamivir phosphate OP treatment of the MRLlpr 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 MRLlpr mice was just completed and sample analysis will begin immediately. The B6.SLE123 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 reportedvalidated 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.
- Medicine and Medical Research