Endothelial activating transcription factor 3 promotes angiogenesis and vascular repair in the mouse retina

内皮活化转录因子 3 促进小鼠视网膜血管生成和血管修复

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作者:Chihiro Ueda, Susumu Sakimoto, Masahito Yoshihara, Toru Takigawa, Akihiko Shiraki, Kaito Yamaguchi, Kosuke Shiki, Nobuhiko Shiraki, Shigetaka Kitajima, Yoshiaki Kubota, Yoko Fukushima, Kohji Nishida

Abstract

Ischemia and pathological angiogenesis in retinal vascular diseases cause serious vision-related problems. However, the transcriptional regulators of vascular repair remain unidentified. Thus, the factors and mechanisms involved in angiogenesis must be elucidated to develop approaches for restoring normal blood vessels. Here, we investigated the effects of the stress response activating transcription factor 3 (ATF3) on angiogenesis and vascular regeneration in vitro and in vivo. ATF3 was expressed specifically in retinal vascular endothelial cells (ECs) during vascular development. Vascular endothelial growth factor stimulation upregulated ATF3 expression in cultured ECs. The downregulated ATF3 expression in ECs caused the deterioration of vascular network formation in vitro and in vivo. Moreover, ATF3 deletion in a model of oxygen-induced retinopathy inhibited retinal vascular repair but not pathological neovascularization. Transcriptome analysis confirmed that high ATF3 expression upregulated the expression of angiogenesis-related genes in ECs. ATF3 may aid vascular repair therapy in retinal vascular diseases.

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