Open AccessKnockdown of dickkopf2 inhibits vascular endothelia growth factor expression through the Wnt/β-catenin signaling pathway in human retinal pigment epithelial cells under hypoxic conditions
Author(s) -
Yu Zhao,
Bin Wu,
Ye Liu,
Jun Xu,
QiChang Yan,
Jinsong Zhang
Publication year - 2018
Publication title -
experimental and therapeutic medicine
Language(s) - English
Resource type - Journals
eISSN - 1792-1015
pISSN - 1792-0981
DOI - 10.3892/etm.2018.5915
Subject(s) - gene knockdown , wnt signaling pathway , vascular endothelial growth factor , microbiology and biotechnology , angiogenesis , biology , vascular endothelial growth factor a , signal transduction , hypoxia inducible factors , cancer research , hypoxia (environmental) , catenin , retinal , chemistry , apoptosis , vegf receptors , gene , biochemistry , organic chemistry , oxygen
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 CoCl 2 -induced expression of hypoxia-inducible factor (HIF)-1α and VEGF in RPE cells. Furthermore, knockdown of DKK2 markedly inhibited the expression of β-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/β-catenin signaling pathway.