Fig. 5

TNF-α upregulated VEGF-D expression and VEGF-D promoter activity downstream of the ERK1/2/AP-1 pathway. a, c The effect of the TNF-α⁄AP-1 signaling pathway on the promoter activity and protein expression of the VEGF-D gene. Transfection with AP-1 siRNA effectively knocked down the expression of AP-1 and p-AP-1 in both NOZ and GBC-SD cells. The protein level and promoter activity of VEGF-D were accordingly reduced irrespective of treatment with TNF-α. b, d The effect of inhibition of MAPK pathway members on the protein expression and promoter activity of VEGF-D. When treated with SP600125 (10 μM), SB203580 (20 μM) or PD98059 (50 μM), the expression of AP-1 and p-AP-1 in both NOZ and GBC-SD cells were reduced. However, the protein expression and promoter activity of VEGF-D were significantly reduced only in the PD98059-treated group. *P < 0.05