Cytochrome P450 2J2 inhibits the proliferation and angiogenesis of retinal vascular endothelial cells by regulating the Notch signaling pathway in a hypoxia-induced retinopathy model.

Abstract

Retinopathy of Prematurity (ROP), a type of retinal neovascularization in premature infants, has become a serious problem that drastically affects the quality of life of premature infants. ROP is associated with angiogenesis and neovascularization. Here, we aimed to explain the function and latent roles of Cytochrome P450 2J2 (CYP2J2) in hypoxia-induced retinopathy in retinal vascular endothelial cells (HRVECs). HRVECs were stimulated with hypoxia for 24 h to establish an in vitro retinopathy model. Cell viability and migration were evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Transwell assays, respectively. Protein and gene expression was determined by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot analysis. We observed that pcDNA3.1(+)-CYP2J2 promoted CYP2J2 and Jagged1 expression, while Dll4 was down-regulated in hypoxia-stimulated HRVECs. Additionally, pcDNA3.1(+)-CYP2J2 inhibited HRVEC viability, reduced PCNA expression, and inhibited the migration of HRVECs. Further, the Notch pathway was inhibited in the Hypoxia+pcDNA3.1(+)-CYP2J2 group. Opposite results were observed upon Terfenadone treatment in hypoxia induced HRVECs. Finally, our findings further verified that DAPT promotes the effects of CYP2J2 on cell viability, migration, and Notch signaling in hypoxia-induced HRVECs, while EDTA reversed the inhibitory effects of CYP2J2 on hypoxia-induced HRVECs. In conclusions, CYP2J2 was found to inhibit the viability and angiogenesis of HRVECs by inhibiting Notch signaling in a hypoxia-induced retinopathy model.

• Authors: Jing Zhang, Qi Xiong, Lin Yang, Yanni Xue, Min Ke, Zhi Li
• Journal: Bioengineered (Bioengineered) Vol. 12 Issue 2 Pg. 10878-10890 (12 2021) ISSN: 2165-5987 [Electronic] United States
• PMID: 34666595 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Notch
• Cytochrome P-450 Enzyme System

Topics

• Apoptosis (physiology)
• Cell Proliferation (physiology)
• Cell Survival (physiology)
• Cells, Cultured
• Cytochrome P-450 Enzyme System (metabolism)
• Down-Regulation (physiology)
• Endothelial Cells (metabolism, pathology)
• Humans
• Hypoxia (metabolism, pathology)
• Neovascularization, Pathologic (metabolism, pathology)
• Receptors, Notch (metabolism)
• Retina (metabolism, pathology)
• Retinal Diseases (metabolism, pathology)
• Signal Transduction (physiology)