Fig. 6.
Netrin-1 activates PPAR pathways in macrophages, and PPAR pathways mediate part of the protective effects of netrin-1. A: netrin-1 increased PPAR, glucorticoid receptor, and RXR pathways as measured by luciferase activity as described in materials and methods. *Significant difference vs. vehicle-treated group (P < 0.05). B: time course of netrin-1-induced expression of PPARα, -β, and -γ in RAW264.7 cells. Netrin-1 significantly increased PPARβ and PPARγ expression but not PPARα expression. *Significant difference vs. 0 h (P < 0.001). C: Western blot analysis of PPARα, -β, and -γ protein expression with netrin-1 treatment. Netrin-1 increased PPARβ and PPARγ but not PPARα protein expression compared with 0 h. D: netrin-1 increased PPARγ ligand production in the presence of TLR4 receptor stimulation. *Signficant difference vs. all other groups (P < 0.01). E: administration of PPARγ antagonist abolished part of netrin-1 protective effects against ischemia-reperfusion injury of the kidney. Significant difference vs. sham: *P < 0.05; #P < 0.05 (n = 4–6).