Ueda Chihiro, Sakimoto Susumu, Yoshihara Masahito, Takigawa Toru, Shiraki Akihiko, Yamaguchi Kaito, Shiki Kosuke, Shiraki Nobuhiko, Kitajima Shigetaka, Kubota Yoshiaki, Fukushima Yoko, Nishida Kohji
Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan.
Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan.
iScience. 2024 Dec 2;28(1):111516. doi: 10.1016/j.isci.2024.111516. eCollection 2025 Jan 17.
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 () on angiogenesis and vascular regeneration and . was expressed specifically in retinal vascular endothelial cells (ECs) during vascular development. Vascular endothelial growth factor stimulation upregulated expression in cultured ECs. The downregulated expression in ECs caused the deterioration of vascular network formation and . Moreover, deletion in a model of oxygen-induced retinopathy inhibited retinal vascular repair but not pathological neovascularization. Transcriptome analysis confirmed that high expression upregulated the expression of angiogenesis-related genes in ECs. may aid vascular repair therapy in retinal vascular diseases.
视网膜血管疾病中的缺血和病理性血管生成会引发严重的视力相关问题。然而，血管修复的转录调节因子仍未明确。因此，必须阐明参与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（）对血管生成和血管再生的影响。在血管发育过程中，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上调了培养的ECs中的表达。ECs中表达下调导致血管网络形成恶化。此外，在氧诱导性视网膜病变模型中的缺失抑制了视网膜血管修复，但不影响病理性新生血管形成。转录组分析证实，高表达上调了ECs中血管生成相关基因的表达。可能有助于视网膜血管疾病的血管修复治疗。
