#3261 SAR131675, A SELECTIVE VEGFR3 INHIBITOR, AMELIORATES RENAL INFLAMMATION AND LYMPHANGIOGENESIS IN THE MURINE LUPUS NEPHRITIS MODEL

Abstract Background and Aims Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune-complex deposits inflammatory cell infiltrations in multiple organs, approximately half of patients have nephritis. Lymphangiogenesis the proliferation pre-existing lymphatic vessels (LVs), which regulate tissue fluid homeostasis immune trafficking, responding to environment. In this study, we evaluated therapeutic effect SAR131672, selective VEGFR3 inhibitor, on murine nephritis model regulating inflammation lymphangiogenesis. Method First, reviewed medical records for biopsy-proven performed an immunohistochemistry study D2-40. For animal experiments, seven eight-week-old male BALB/c mice were used. The back area's skin was shaved treated topically three times per week, with 100 μg resiquimod μl acetone eight weeks concomitantly treatment SAR 131672 oral gavage. We renal histology immunofluorescent cells vessels. also cytokines chemokines, lymphangiogenic factors qRT-PCR. Results human found that higher activity index, more D2-40(+) are expressed tubulointerstitial areas. topical Balb/c induces lupus-like symptoms such as weight loss, splenomegaly, glomerular complexes IgG, IgM, C3 staining. Histologically, mesangial increased areas noted H&E stain. Inhibition SAR131672 decreases LYVE-1(+) pro-inflammatory chemokines ICAM-1, VCAM-1, MCP-1, CCL19, CCL21, CCR7, CXCL13, BAFF mRNA levels compared vehicle-treated group. Treatment chemokine. Conclusion resiquimod-induced