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.