June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Endothelial ATF3 expression promotes angiogenesis in murine retina
Author Affiliations & Notes
  • Susumu Sakimoto
    Osaka Univ School of Medicine, Japan
  • Chihiro Ueda
    Osaka Univ School of Medicine, Japan
  • Akihiko Shiraki
    Osaka Univ School of Medicine, Japan
  • Toru Takigawa
    Osaka Univ School of Medicine, Japan
  • Kaito Yamaguchi
    Osaka Univ School of Medicine, Japan
  • Nobuhiko Shiraki
    Osaka Univ School of Medicine, Japan
  • Shigetaka Kitajima
    Tokyo Ika Shika Daigaku, Bunkyo-ku, Tokyo, Japan
  • Yoshiaki Kubota
    Keio Gijuku Daigaku, Minato-ku, Tokyo, Japan
  • Yoko Fukushima
    Osaka Univ School of Medicine, Japan
  • Kohji Nishida
    Osaka Univ School of Medicine, Japan
  • Footnotes
    Commercial Relationships   Susumu Sakimoto None; Chihiro Ueda None; Akihiko Shiraki None; Toru Takigawa None; Kaito Yamaguchi None; Nobuhiko Shiraki None; Shigetaka Kitajima None; Yoshiaki Kubota None; Yoko Fukushima Otsuka Pharmaceutical., Code E (Employment); Kohji Nishida None
  • Footnotes
    Support  JP21gm1210004h0004, Grant-in-Aid for Scientific Research (C) JP21K09674
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4477. doi:
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    • Get Citation

      Susumu Sakimoto, Chihiro Ueda, Akihiko Shiraki, Toru Takigawa, Kaito Yamaguchi, Nobuhiko Shiraki, Shigetaka Kitajima, Yoshiaki Kubota, Yoko Fukushima, Kohji Nishida; Endothelial ATF3 expression promotes angiogenesis in murine retina. Invest. Ophthalmol. Vis. Sci. 2023;64(8):4477.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Activating transcriptional factor 3 (ATF3), a member of the ATF/CREB family of transcription factors reportedly takes part in various stress response. This study aimed to investigate whether ATF3 promotes angiogenesis in mice retina.

Methods : To confirm the expression of ATF3 in vascular endothelial cells (ECs), we performed qPCR on CD31+ CD45- cells that were sorted from retina at postnatal 5 days (P5) and of oxygen induced retinopathy (OIR) model at P17 in C57BL/6 mice. qPCR was also performed in mRNA from Human Retinal Microvascular Endothelial Cells (HRMECs) which were stimulated by VEGF in vitro. Tube formation assays on Matrigel were tested using HRMECs with ATF3 knockdown. We generated EC specific conditional ATF3 knockout (ATF3-ECKO) mice which were obtained by crossing cdh5-BAC-CreERT2 mice and ATF3 flox mice, and then we analyzed postnatal angiogenesis in retina at P5 by immunohistochemical (IHC) analysis for ECs.

Results : ATF3 mRNA expression are more than ten times higher in CD31+ CD45- ECs than CD31- CD45- non-ECs at P5 retinas (P<0.01). Three times higher expression of ATF3 was also detected in ECs from OIR mice retina compared to control normoxic mice at P17 (p<0.05). qPCR analysis also detected increased ATF3 expression in HRMECs when stimulated by VEGF in vitro (p<0.01). Tube-formation analysis using HRMECs with ATF3 knockdown cultured on Matrigel revealed that decrease of ATF3 expression caused less density of tubes (p<0.001). IHC analysis for CD31 showed that retinas from ATF3-ECKO mice showed less vascular progression length, branch point and tip cells compared to WT mice (P < 0.05, P < 0.01 and P < 0.001, respectively).

Conclusions : ATF3 expression in retinal ECs were detected both in vitro and in vivo. Moreover, ATF3 deficient mice showed impaired angiogenesis during postnatal period. These results indicated that stress response transcriptional factor ATF3 potentially promotes angiogenesis in retina.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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