Knockdown of dickkopf2 inhibits vascular endothelia growth factor expression through the Wnt/[beta]-catenin signaling pathway in human retinal pigment epithelial cells under hypoxic conditions

Hypoxia has been demonstrated to be a proangiogenic factor that induces vascular endothelial growth factor (VEGF) in retinal pigment epithelial (RPE) cells. Dickkopf2 (DKK2), originally known as Wnt antagonist, has recently been demonstrated to have an important regulatory role in angiogenesis; however, the specific role of DKK2 in RPE cells is not known. In the present study, the effects of DKK2 on VEGF expression under hypoxic conditions were investigated, as well as the molecular mechanisms involved. The results demonstrated that the expression of DKK2 was markedly increased under hypoxic conditions compared with normoxic conditions. Knockdown of DKK2 markedly attenuated the Co[Cl.sub.2]-induced expression of hypoxia-inducible factor (HIF)-1[alpha] and VEGF in RPE cells. Furthermore, knockdown of DKK2 markedly inhibited the expression of p-catenin induced by hypoxia. In conclusion, the findings of the present study demonstrate that knockdown of DKK2 inhibits the hypoxia-induced production of VEGF by suppressing the activation of the Wnt/p-catenin signaling pathway.