Fig. 4. CCL19 suppresses angiogenesis through ERK/ELK-1/HIF-1α/VEGFA inhibition.

a and b CCL19 inhibits the expression of HIF-1α and VEGF-A in HUVEC. No differences are observed in p-c-jun/AP-1 and c-jun. c 2-MeOE2 inhibits the expression of VEGF-A. d and e Results of 3D sprouting angiogenesis assays showed the inhibitory roles of 2-MeOE2 on indicated HUVEC (magnification, 200×). f and g CCL19 inhibits the phosphorylation of ERK and Akt in HUVEC. No differences are observed in STAT3 or JNK pathway. h and i Inhibition of the ERK pathway using U0126 downregulates p-Elk-1, HIF-1a, and VEGF-A expression. Inhibition of the AKT pathway using LY294002 is not able to change the expression of HIF-1a and VEGF-A. j Results of 3D sprouting angiogenesis assays showed the inhibitory roles of U0126 on indicated HUVEC (magnification, 200×). Average distance leading cells invaded from monolayer and average length of extended processes were used to evaluate the sprouting responses of HUVEC. Data represent the mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001