PUBLICATION
Opticin Ameliorates Hypoxia-Induced Retinal Angiogenesis by Suppression of Integrin α2-I Domain-Collagen Complex Formation and RhoA/ROCK1 Signaling
- Authors
- Liu, X., Xing, Y., Liu, X., Zeng, L., Ma, J.
- ID
- ZDB-PUB-220111-15
- Date
- 2022
- Source
- Investigative ophthalmology & visual science 63: 13 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Signal Transduction
- RNA/genetics
- Zebrafish Proteins/biosynthesis
- Zebrafish Proteins/genetics*
- Zebrafish
- Disease Models, Animal
- Animals
- Retinal Neovascularization/genetics*
- Retinal Neovascularization/metabolism
- Retinal Neovascularization/pathology
- Proteoglycans/biosynthesis
- Proteoglycans/genetics*
- Monomeric GTP-Binding Proteins/biosynthesis
- Monomeric GTP-Binding Proteins/genetics*
- rho-Associated Kinases/biosynthesis
- rho-Associated Kinases/genetics*
- Gene Expression Regulation*
- Integrin alpha2/biosynthesis
- Integrin alpha2/genetics*
- PubMed
- 35006271 Full text @ Invest. Ophthalmol. Vis. Sci.
Citation
Liu, X., Xing, Y., Liu, X., Zeng, L., Ma, J. (2022) Opticin Ameliorates Hypoxia-Induced Retinal Angiogenesis by Suppression of Integrin α2-I Domain-Collagen Complex Formation and RhoA/ROCK1 Signaling. Investigative ophthalmology & visual science. 63:13.
Abstract
Purpose It was previously demonstrated that opticin (OPTC) inhibits the collagen-induced promotion of bioactivities of human retinal vascular endothelial cells (hRVECs). The present in vivo study aimed to further investigate the regulatory role of opticin in vitreous collagen-mediated retinal neovascularization and to elucidate its regulatory mechanisms with regard to integrin α2-I domain-GXXGER complex formation and RhoA/ROCK1 signal change. The regulatory role of Mg2+ on integrin α2-I domain-GXXGER complex formation in the above process was also investigated.
Methods The zebrafish model of hypoxia-induced retinopathy was established, and OPTC-overexpressing plasmids were intravitreally injected to assess the antiangiogenesis effect of opticin. The regulatory role of opticin in integrin α2-I domain-GXXGER complex formation in vivo was analyzed by mass spectrometry. The mRNA and protein expression of RhoA/ROCK1 were examined. The concentration of Mg2+ as an activator of the integrin α2-I domain-GXXGER complex was measured. Solid-phase binding assays were performed to investigate the interference of opticin in integrin α2 collagen binding and the regulatory role of Mg2+ in that process.
Results Opticin and OPTC-overexpressing plasmid injection reduced retinal neovascularization in the zebrafish model of hypoxia-induced retinopathy. Mass spectrometry revealed that opticin could inhibit integrin α2-I domain-GXXGER complex formation. The Mg2+ concentration was also decreased by opticin, which was another indication of the complex activation. Injection of OPTC-overexpressing plasmids inhibited mRNA and the protein expression of RhoA/ROCK1 in the zebrafish model of hypoxia-induced retinopathy. The solid-phase binding assay revealed that opticin could block integrin α2-collagen I binding in the presence of Mg2+.
Conclusions Opticin exerts its antiangiogenesis effect by interfering in the Mg2+-modulated integrin α2-I domain-collagen complex formation and suppressing the downstream RhoA/ ROCK1 signaling pathway.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping