Sodium Butyrate Inhibits Neovascularization Partially via TNXIP/VEGFR2 Pathway

• Published in: Oxidative medicine and cellular longevity Vol. 2020; no. 2020; pp. 1 - 13
• Main Authors: Chen, Haoyu, Liang, Jiajian, Huang, Shaofen, Xu, Yanxuan, Chen, Min, Xiao, Xiaoqiang, Cao, Yingjie
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 2020; Hindawi; Hindawi Limited
• Subjects: Angiogenesis; Animals; Antibodies; Butyric Acid - pharmacology; Carrier Proteins - metabolism; Cell cycle; Cell growth; Choroidal Neovascularization - drug therapy; Choroidal Neovascularization - metabolism; Choroidal Neovascularization - pathology; Diabetic retinopathy; Gene expression; Growth factors; Human Umbilical Vein Endothelial Cells - metabolism; Human Umbilical Vein Endothelial Cells - pathology; Humans; Lasers; Mice; Plasmids; Proteins; Signal Transduction - drug effects; Thioredoxins - metabolism; Vascular Endothelial Growth Factor Receptor-2 - metabolism; United States > US
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2020/6415671

Control of neovascularization with small molecules is a promising tactics. Here, we tested the roles of sodium butyrate (NaBu) on the neovascularization and primary explained its underlining molecular links. We used models including cell and ex vivo culture of choroid and mouse, as well as the biochemical and cellular techniques, to confirm our hypothesis. We found that treating HUVEC cells with NaBu (both 2.5 mM and 5 mM) significantly inhibited its ability in tube formation and proliferation. This inhibitory effect was also observed in choroid sprouting experiments, compared to the control. Interestingly, the choroid sprouting suppressed by NaBu can proliferate again after removing it, indicating that the cell cycle progression might be arrested. The laser-induced choroid neovascularization (CNV) was significantly alleviated by assessing the CNV size (decreased to 0.73 fold) in contrast with the vehicle control group after 2.5 mM NaBu injection for 7 days. Mechanistically, we found an enhanced TXNIP expression in response to NaBu treatment in all the three models. Overexpressing TXNIP in HUVEC cells blocked its tube formation and inhibited its proliferation; on the other hand, knocking down its expression with shRNA reversed those phenotypes in context of NaBu treatment. Further investigation showed the expression of VEGF receptor 2 (VEGFR2) in HUVEC cells was regulated by TXNIP undergoing NaBu treatment. We therefore argued that NaBu inhibited neovascularization partially through TXNIP-regulated VEGFR2 signal pathway.