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

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-01-17 DOI:10.1016/j.isci.2024.111516

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

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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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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。

视网膜血管疾病的缺血和病理性血管生成引起严重的视力问题。然而，血管修复的转录调节因子仍未被发现。因此，必须阐明血管生成的因素和机制，以开发恢复正常血管的方法。在此，我们研究了应激反应激活转录因子3 （ATF3）对体外和体内血管生成和血管再生的影响。在血管发育过程中，ATF3在视网膜血管内皮细胞（ECs）中特异性表达。血管内皮生长因子刺激可上调培养内皮细胞中ATF3的表达。体外和体内实验中，ECs中ATF3表达下调导致血管网络形成恶化。此外，在氧诱导视网膜病变模型中，ATF3缺失抑制视网膜血管修复，但不抑制病理性新生血管形成。转录组分析证实，ATF3的高表达上调了内皮细胞血管生成相关基因的表达。ATF3可能有助于视网膜血管疾病的血管修复治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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