PUBLICATION
Erianin Controls Collagen-Mediated Retinal Angiogenesis via the RhoA/ROCK1 Signaling Pathway Induced by the alpha2/beta1 Integrin-Collagen Interaction
- Authors
- Li, X., Liu, X., Xing, Y., Zeng, L., Liu, X., Shen, H., Ma, J.
- ID
- ZDB-PUB-220126-19
- Date
- 2022
- Source
- Investigative ophthalmology & visual science 63: 27 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Bibenzyls/pharmacology*
- Cell Movement
- Cells, Cultured
- Collagen/metabolism
- Disease Models, Animal
- Gene Expression Regulation*
- Integrin alpha1/biosynthesis
- Integrin alpha1/genetics*
- Integrin beta1/biosynthesis
- Integrin beta1/genetics*
- Monomeric GTP-Binding Proteins/biosynthesis
- Monomeric GTP-Binding Proteins/genetics*
- Phenol/pharmacology*
- Retinal Neovascularization/genetics*
- Retinal Neovascularization/metabolism
- Retinal Neovascularization/pathology
- Signal Transduction
- Zebrafish
- Zebrafish Proteins/biosynthesis
- Zebrafish Proteins/genetics*
- rho-Associated Kinases/biosynthesis
- rho-Associated Kinases/genetics*
- PubMed
- 35060996 Full text @ Invest. Ophthalmol. Vis. Sci.
Citation
Li, X., Liu, X., Xing, Y., Zeng, L., Liu, X., Shen, H., Ma, J. (2022) Erianin Controls Collagen-Mediated Retinal Angiogenesis via the RhoA/ROCK1 Signaling Pathway Induced by the alpha2/beta1 Integrin-Collagen Interaction. Investigative ophthalmology & visual science. 63:27.
Abstract
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 α2 and β1 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 α2 and β1 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 α2 and β1 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 α2 and β1 integrin-collagen interactions. These findings suggest that erianin has the therapeutic potential on intraocular collagen-mediated retinal angiogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping