Andrographolide suppresses hypoxia-induced embryonic hyaloid vascular system development through HIF-1a/VEGFR2 signaling pathway

• Published in: Frontiers in cardiovascular medicine Vol. 10; p. 1090938
• Main Authors: Jin, Zhong, Guo, Qiru, Wang, Zheng, Wu, Xiao, Hu, Wangming, Li, Jiali, Li, Hongfei, Zhu, Song, Zhang, Haidi, Chen, Zixian, Xu, Huan, Shi, Liangqin, Yang, Lan, Wang, Yong
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 08.02.2023
• Subjects: andrographolide; Cardiovascular Medicine; embryonic hyaloid vasculature development; HIF-1a; hypoxia; VEGF; hypoxia; HIF-1a; VEGF; embryonic hyaloid vasculature development; andrographolide
• ISSN: 2297-055X; 2297-055X
• DOI: 10.3389/fcvm.2023.1090938

Ocular abnormalities and the development of retinal vasculature may cause postnatal retinopathy. In the past decade, tremendous progress has been made in identifying the mechanisms that regulate retina vasculature. However, the means of regulating embryonic hyaloid vasculature development is largely unknown. This study aims to determine whether and how andrographolide regulates embryonic hyaloid vasculature development. Murine embryonic retinas were used in this study. Whole mount isolectin B4 (IB4) staining, hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and immunofluorescence staining (IF) were performed to determine whether andrographolide is critical for embryonic hyaloid vasculature development. BrdU incorporation assay, Boyden chamber migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay were performed to evaluate whether andrographolide regulates the proliferation and migration of vascular endothelial cells. Molecular docking simulation and Co-immunoprecipitation assay were used to observe protein interaction. Hypoxia conditions exist in murine embryonic retinas. Hypoxia induces HIF-1a expression; high-expressed HIF-1a interacts with VEGFR2, resulting in the activation of the VEGF signaling pathway. Andrographolide suppresses hypoxia-induced HIF-1a expression and, at least in part, interrupts the interaction between HIF-1a and VEGFR2, causing inhibiting endothelial proliferation and migration, eventually inhibiting embryonic hyaloid vasculature development. Our data demonstrated that andrographolide plays a critical role in regulating embryonic hyaloid vasculature development.