Overexpression of Twist1 in vascular endothelial cells promotes pathological retinal angiogenesis in mice

	Overexpression of Twist1 in vascular endothelial cells promotes pathological retinal angiogenesis in mice
	Zhang, L; Zhang, SS; Wang, KF; Li, YH; Xu, HJ; Sun, KX; Ma, S; Leng, HM; Chen, SZ; Jia, WJ
刊名	ZOOLOGICAL RESEARCH
	2022
卷号	43 期号:1 页码:64
英文摘要	Retinal angiogenesis is a critical process for normal retinal function. However, uncontrolled angiogenesis can lead to pathological neovascularization (NV), which is closely related to most irreversible blindness-causing retinal diseases. Understanding the molecular basis behind pathological NV is important for the treatment of related diseases. Twist-related protein 1 (TWIST1) is a well-known transcription factor and principal inducer of epithel-ialmesenchymal transition (EMT) in many human cancers. Our previous study showed that Twist1 expression is elevated in pathological retinal NV. To date, however, the role of TWIST1 in retinal pathological angiogenesis remains to be elucidated. To study the role of TWIST1 in pathological retinal NV and identify specific molecular targets for antagonizing pathological NV, we generated an inducible vascular endothelial cell (EC)-specific Twist1 transgenic mouse model (Tg-Twist1(iEC+)). Whole-mount retinas from Tg-Twist(1iEC+) mice showed retarded vascular progression and increased vascular density in the front end of the growing retinal vasculature, as well as aneurysm-like pathological retinal NV. Furthermore, overexpression of Twist1 in the ECs promoted cell proliferation but disturbed cell polarity, thus leading to uncontrolled retinal angiogenesis. TWIST1 promoted pathological NV by activating the Wnt/beta-catenin signaling pathway and inducing the expression of NV formation-related genes, thereby acting as a 'valve' in the regulation of pathological angiogenesis. This study identified the critical role of TWIST1 in retinal pathological NV, thus providing a potential therapeutic target for pathological NV.
内容类型	期刊论文
源URL	[http://210.75.249.4/handle/363003/61318]
专题	西北高原生物研究所_中国科学院西北高原生物研究所
推荐引用方式 GB/T 7714	Zhang, L,Zhang, SS,Wang, KF,et al. Overexpression of Twist1 in vascular endothelial cells promotes pathological retinal angiogenesis in mice[J]. ZOOLOGICAL RESEARCH,2022,43(1):64.
APA	Zhang, L.,Zhang, SS.,Wang, KF.,Li, YH.,Xu, HJ.,...&Li, J.(2022).Overexpression of Twist1 in vascular endothelial cells promotes pathological retinal angiogenesis in mice.ZOOLOGICAL RESEARCH,43(1),64.
MLA	Zhang, L,et al."Overexpression of Twist1 in vascular endothelial cells promotes pathological retinal angiogenesis in mice".ZOOLOGICAL RESEARCH 43.1(2022):64.