June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Dexamethasone attenuates hypoxia- and diabetes-induced retinal galectin-1 expression via reducing hypoxia-inducible factor-1α protein in vitro and in vivo
Author Affiliations & Notes
  • Atsuhiro Kanda
    Ophthalmology, Hokkaido University, Sapporo, HOKKAIDO, Japan
  • Ikuyo Hirose
    Ophthalmology, Hokkaido University, Sapporo, HOKKAIDO, Japan
  • Shiho Yoshida
    Ophthalmology, Hokkaido University, Sapporo, HOKKAIDO, Japan
  • Miyuki Murata
    Ophthalmology, Hokkaido University, Sapporo, HOKKAIDO, Japan
  • Susumu Ishida
    Ophthalmology, Hokkaido University, Sapporo, HOKKAIDO, Japan
  • Footnotes
    Commercial Relationships   Atsuhiro Kanda, Bayer AG (F), Bayer Yakuhin Ltd (F); Ikuyo Hirose, None; Shiho Yoshida, None; Miyuki Murata, None; Susumu Ishida, None
  • Footnotes
    Support  Bayer Yakuhin Ltd, Bayer AG, MEXT KAKENHI Grant Number 19K09944 (to A.K.).
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 747. doi:
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      Atsuhiro Kanda, Ikuyo Hirose, Shiho Yoshida, Miyuki Murata, Susumu Ishida; Dexamethasone attenuates hypoxia- and diabetes-induced retinal galectin-1 expression via reducing hypoxia-inducible factor-1α protein in vitro and in vivo. Invest. Ophthalmol. Vis. Sci. 2020;61(7):747.

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

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Abstract

Purpose : Galectin-1/LGALS1, a newly recognized inflammation- and hypoxia-induced angiogenic factor, contributes to the pathogenesis of diabetic retinopathy (DR). Recently, we revealed an interleukin-1β-induced inflammatory pathway to produce galectin-1 in retinal Müller glial cells, which glucocorticoids suppressed via transactivation and transrepression [Hirose I et al. 2019 J Cell Mol Med.]. Here, we show dexamethasone’s inhibitory mechanism for hypoxia-induced galectin-1/LGALS1 expression in Müller glial cells.

Methods : Immunoblot and real-time PCR analyses were performed to measure protein and mRNA expression levels in human Müller glial (MIO-M1) cells and the retina of mice with streptozotocin-induced diabetes. Reporter assay was performed to determine the transcription-activating function of LGALS1 promotor.

Results : Hypoxia-induced increases in galectin-1/LGALS1 expression (fold change = 2.1) and promoter activity (fold change = 1.5) were suppressed by dexamethasone (fold change = 1.3 for gene expression, 1.1 for promoter activity, p < 0.05). Dexamethasone suppressed hypoxia-induced levels of hypoxia-inducible factor (HIF)-1α protein and DNA-binding activity (fold change with hypoxia = 2.5, plus dexamethasone = 1.4, p < 0.05) in Müller glial cells. Moreover, the suppressive effect of dexamethasone on LGALS1 mRNA levels was reversed by pretreatment with the glucocorticoid receptor antagonist RU486 (fold change = 2.2, p < 0.05). Application of dexamethasone to mice significantly reduced diabetes-induced retinal galectin-1/Lgals1 expression (fold change = 4.6, plus dexamethasone = 2.5, p < 0.05) together with HIF-1α protein levels.

Conclusions : Our present findings demonstrated the inhibitory action of dexamethasone on HIF-1α-mediated galectin-1/LGALS1expression, which would be important with respect to the anti-inflammatory and -angiogenic intervention in DR patients.

This is a 2020 ARVO Annual Meeting abstract.

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