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Oxidative stress upregulates Wnt signaling in human retinal microvascular endothelial cells through activation of disheveled
Author(s) -
Zhang Chi,
Tannous Elizabeth,
Zheng Jie J.
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28679
Subject(s) - wnt signaling pathway , oxidative stress , microbiology and biotechnology , downregulation and upregulation , lrp5 , signal transduction , retinal , frizzled , beta catenin , cell signaling , neovascularization , endothelial stem cell , cancer research , angiogenesis , chemistry , biology , endocrinology , biochemistry , in vitro , gene
Abnormal retinal neovascularization associated with various retinopathies can result in irreversible vision loss. Although the mechanisms involved in this occurrence is unclear, increasing evidence suggests that aberrant Wnt signaling participates in the pathogenesis of abnormal neovascularization. Because Wnt signaling upregulation can be induced by oxidative stress through the activation of disheveled (DVL), a key molecule in the Wnt signaling pathway, we investigated whether oxidative stress can activate Wnt signaling and induce angiogenic phenotypes in human retinal microvascular endothelial cells (HRMECs). We found that increased Wnt signaling activity, as well as enhanced angiogenic phenotypes, such as tube formation and cell migration, were detected in the hydrogen peroxide‐treated HRMECs. Moreover, these effects were effectively suppressed by a small‐molecule Wnt inhibitor targeting the PDZ domain of DVL. Therefore, we propose that targeting abnormal Wnt signaling at the DVL level with a small‐molecule inhibitor may represent a novel approach in retinal neovascularization treatment and prevention.