Effect of genistein on regenerative angiogenesis using zebrafish as model organism

Abstract

We examined the effects of phytoestrogen genistein on zebrafish caudal fin regeneration and found that genistein could inhibit fin generation in μM concentration. Fish were injected with varying concentrations (10–100 μM) of genistein for 5 days after caudal fin amputation, and regeneration of the fin was evaluated by analyzing caudal fin length and newly formed vascular region. Regeneration of amputated fins was inhibited or delayed to the maximum of 64.7% in dorsal region, 63.35% in cleft region and 66.54% in ventral region after genistein treatment unlike the control that completely regenerated their fins after 5 days post-amputation (DPA). PCR data showed a clear reduction in vascular endothelial growth factor (VEGF) expression on exposure to genistein while a complete inhibition was observed with sunitinib (SU 11652) an inhibitor of VEGF signaling. The ability of genistein to inhibit regenerative angiogenesis of caudal fin probably by down regulating VEGF, the key player of angiogenesis and the results obtained with SU 11652 is suggestive of the involvement of VEGF signaling during regeneration. These results demonstrate that zebrafish could be a good model in elucidating molecular mechanisms that are responsible for fin regeneration.