Overexpression of Twist1 in vascular endothelial cells promotes pathological retinal angiogenesis in mice Zhang-2022
Normal retinal function requires angiogenesis. Uncontrolled angiogenesis can lead to pathological neovascularization (NV), which causes most retinal blindness. Pathological NV is important for treating related diseases. Twist-related protein 1 (TWIST1) is a transcription factor and EMT inducer in many cancers. Twist1 is upregulated in pathological retinal NV, according to our study. TWIST1's role in retinal pathological angiogenesis is unknown. To study the role of TWIST1 in pathological retinal NV and identify molecular targets for antagonizing pathological NV, we generated an inducible EC-specific Twist1 transgenic mouse model (Tg-Twist1iEC+). Whole-mount retinas from Tg-Twist1iEC+ mice showed retarded vascular progression, increased vascular density in the growing retinal vasculature, and aneurysm-like retinal NV. Overexpression of Twist1 in ECs led to uncontrolled retinal angiogenesis by promoting cell proliferation but disturbing cell polarity. TWIST1 promoted pathological NV by activating the Wnt/-catenin signaling pathway and inducing NV formation-related genes, acting as a 'valve' in pathological angiogenesis. This study identified TWIST1's role in retinal pathological NV, providing a potential therapeutic target.
Zhang L, Zhang SS, Wang KF, Li YH, Xu HJ, Sun KX, Ma S, Leng HM, Chen SZ, Jia WJ, Zhu XJ, Li J. Overexpression of Twist1 in vascular endothelial cells promotes pathological retinal angiogenesis in mice. Zool Res. 2022 Jan 18;43(1):64-74. doi: 10.24272/j.issn.2095-8137.2021.281. PMID: 34845879; PMCID: PMC8743260.
