Erianin Controls Collagen-Mediated Retinal Angiogenesis via the RhoA/ROCK1 Signaling Pathway Induced by the alpha2/beta1 Integrin-Collagen Interaction

被引：10

作者：

Li, Xueke ^{[1
]}

Liu, Xiaoxue ^{[1
]}

Xing, Yue ^{[1
]}

Zeng, Lingyan ^{[1
]}

Liu, Xin ^{[1
]}

Shen, Huangxuan ^{[1
]}

Ma, Jin ^{[1
]}

机构：

[1] Sun Yat sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Peoples R China

来源：

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE | 2022年 / 63卷 / 01期

关键词：

erianin; retinal neovascularization; collagen; alpha 2 and beta 1 integrin; RhoA/ROCK1; pathway; INDUCED PATHOLOGICAL ANGIOGENESIS; GENE-EXPRESSION; IN-VIVO; VASCULAR DEVELOPMENT; CELL APOPTOSIS; HYPOXIA; VITRO;

D O I：

10.1167/iovs.63.1.27

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

PURPOSE. Erianin has been reported to inhibit tumor activity by suppressing the expression of integrins. It is hypothesized that erianin can inhibit retinal neovascularization in collagen by suppressing the expression of integrins. With an aim to test this hypothesis, the regulation of erianin on collagen-mediated retinal angiogenesis via the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK1) signaling pathway induced by alpha 2 and beta 1 integrin-collagen interactions was investigated. METHODS. The effects of erianin on human retinal vascular endothelial cells (HRVECs) were assessed in vitro using a hypoxia model in a three-dimensional cell culture induced by cobalt (II) chloride (CoCl2). A hypoxia-induced retinopathy model in adult zebrafish and zebrafish embryos was established to assess the antiangiogenic effect of erianin with and without vitreous collagen in vivo. The expression of alpha 2 and beta 1 integrin and RhoA/ROCK1 pathway in HRVECs and zebrafish retinas were analyzed. RESULTS. In vitro, collagen improved the angiogenic potential of HRVECs, including migration, adhesion, and tube formation, in a three-dimensional cell culture model. Erianin suppressed the angiogenic processes of the CoCl2-induced hypoxia HRVEC model in a concentration-dependent manner. In vivo, erianin reduced retinal angiogenesis in the hypoxia-induced retinopathy model in adult and embryo zebrafish. Erianin inhibited the expression of alpha and beta 1 integrin and RhoA/ROCK1 in a hypoxia-induced model in vitro in three-dimensional cell culture and in vivo in adult zebrafish. CONCLUSIONS. Collagen-mediated retinal angiogenesis may be regulated by erianin via the RhoA/ROCK1 signaling pathway induced by alpha 2 and beta 1 integrin-collagen interactions. These findings suggest that erianin has the therapeutic potential on intraocular collagenmediated retinal angiogenesis.

引用

页数：18

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