Glucocorticoid receptor inhibits Müller glial galectin-1 expression via DUSP1-dependent and -independent deactivation of AP-1 signalling.

Hirose, Ikuyo; Kanda, Atsuhiro; Noda, Kousuke; Ishida, Susumu

Glucocorticoid receptor inhibits Müller glial galectin-1 expression via DUSP1-dependent and -independent deactivation of AP-1 signalling.

Hirose, Ikuyo; Kanda, Atsuhiro; Noda, Kousuke et al.

Journal of cellular and molecular medicine, 2019, 23(10), 6785-6796

Permalink : https://hdl.handle.net/2115/76169

このアイテムのアクセス数:748件（2026-08-15 19:02 集計）

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ファイル	フォーマット	サイズ	閲覧回数	説明
https://doi.org/10.1111/jcmm.14559			19

論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/76169
タイトル	Glucocorticoid receptor inhibits Müller glial galectin-1 expression via DUSP1-dependent and -independent deactivation of AP-1 signalling.
著者	Hirose, Ikuyo ; Kanda, Atsuhiro ; Noda, Kousuke ; Ishida, Susumu
著者名 Hirose, Ikuyo
e-Rad_Researcher 80342707 著者名 Kanda, Atsuhiro
e-Rad_Researcher 90296666 著者名 Noda, Kousuke
e-Rad_Researcher 10245558 著者名 Ishida, Susumu
言語	英語
キーワード	activator protein‐1
	betic retinopathy, dual
	pecificity phosphatase 1
	galectin‐1
	glucocorticoid receptor
	interleukin‐1β
	Müller glia
	transactivation
	transrepression
発行日	2019-10
出版者	John Wiley & Sons
収録物名	Journal of cellular and molecular medicine
巻(号)	23(10)
ページ	6785-6796
抄録	Galectin-1/LGALS1 is a hypoxia-induced angiogenic factor associated with diabetic retinopathy (DR). Recently, we elucidated a hypoxia-independent pathway to produce galectin-1 in Müller glial cells stimulated by interleukin (IL)-1β. Here we revealed glucocorticoid receptor (GR)-mediated inhibitory mechanisms for Müller glial galectin-1/LGALS1 expression. Activator protein (AP)-1 site in the LGALS1 enhancer region, to which activating transcription factor2, c-Fos and c-Jun bind, was shown to be essential for IL-1β-induced galectin-1/LGALS1 expression in Müller cells. Ligand (dexamethasone or triamcinolone acetonide)-activated GR induced dual specificity phosphatase (DUSP)1 expression via the glucocorticoid response element and attenuated IL-1β-induced galectin-1/LGALS1 expression by reducing phosphorylation of these AP-1 subunits following AKT and extracellular signal-regulated kinase (ERK)1/2 deactivation. Moreover, activated GR also caused DUSP1-independent down-regulation of IL-1β-induced LGALS1 expression via its binding to AP-1. Administration of glucocorticoids to mice attenuated diabetes-induced retinal galectin-1/Lgals1 expression together with AKT/AP-1 and ERK/AP-1 pathways. Supporting these in vitro and in vivo findings, immunofluorescence analyses showed co-localization of galectin-1 with GR and phosphorylated AP-1 in DUSP1-positive glial cells in fibrovascular tissues from patients with DR. Our present data demonstrated the inhibitory effects of glucocorticoids on glial galectin-1 expression via DUSP1-dependent and -independent deactivation of AP-1 signalling (transactivation and transrepression), highlighting therapeutic implications for DR.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 4.0 International
PISSN	1582-4934
関連情報	PMID 31328390
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1111/jcmm.14559