Volume 43 Issue 1
Jan.  2022
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Lin Zhang, Shan-Shan Zhang, Kai-Fang Wang, Yi-Hui Li, Hui-Juan Xu, Kuan-Xiang Sun, Shi Ma, Hong-Mei Leng, Si-Zhu Chen, Wen-Jing Jia, Xian-Jun Zhu, Jie Li. Overexpression of Twist1 in vascular endothelial cells promotes pathological retinal angiogenesis in mice. Zoological Research, 2022, 43(1): 64-74. doi: 10.24272/j.issn.2095-8137.2021.281
Citation: Lin Zhang, Shan-Shan Zhang, Kai-Fang Wang, Yi-Hui Li, Hui-Juan Xu, Kuan-Xiang Sun, Shi Ma, Hong-Mei Leng, Si-Zhu Chen, Wen-Jing Jia, Xian-Jun Zhu, Jie Li. Overexpression of Twist1 in vascular endothelial cells promotes pathological retinal angiogenesis in mice. Zoological Research, 2022, 43(1): 64-74. doi: 10.24272/j.issn.2095-8137.2021.281

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

doi: 10.24272/j.issn.2095-8137.2021.281
#Authors contributed equally to this work
Funds:  This study was supported by the National Natural Science Foundation of China (82071009, 81700841) and by the Grant from Chinese Academy of Medical Sciences (2019-I2M-5-032)
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  • Corresponding author: E-mail: doctorjacklee@163.com
  • Received Date: 2021-10-16
  • Accepted Date: 2021-11-29
  • Available Online: 2021-11-29
  • Publish Date: 2022-01-18
  • 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 epithelial-mesenchymal 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-Twist1iEC+). Whole-mount retinas from Tg-Twist1iEC+ 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/β-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.
  • #Authors contributed equally to this work
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