Glucocorticoid-transactivated TSC22D3 attenuates hypoxia- and diabetes-induced Muller glial galectin-1 expression via HIF-1 alpha destabilization

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

Glucocorticoid-transactivated TSC22D3 attenuates hypoxia- and diabetes-induced Muller glial galectin-1 expression via HIF-1 alpha destabilization

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

Journal of cellular and molecular medicine, 2020, 24(8), 4589-4599

Permalink : https://hdl.handle.net/2115/78420

このアイテムのアクセス数:691件（2026-10-06 09:51 集計）

閲覧可能ファイル

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.15116			40

論文情報

ファイル出力 EndNote Basic出力 Mendeley出力

アクセス権	open access
URI	https://hdl.handle.net/2115/78420
タイトル	Glucocorticoid-transactivated TSC22D3 attenuates hypoxia- and diabetes-induced Muller glial galectin-1 expression via HIF-1 alpha destabilization
著者	Kanda, Atsuhiro ; Hirose, Ikuyo ; Noda, Kousuke ; Murata, Miyuki ; Ishida, Susumu
e-Rad_Researcher 80342707 著者名 Kanda, Atsuhiro
著者名 Hirose, Ikuyo
e-Rad_Researcher 90296666 著者名 Noda, Kousuke
e-Rad_Researcher 50423752 著者名 Murata, Miyuki
e-Rad_Researcher 10245558 著者名 Ishida, Susumu
言語	英語
キーワード	diabetic retinopathy
	galectin-1
	glucocorticoid
	HIF-1 alpha
	hypoxia
	Muller glia
	transactivation
発行日	2020-04
出版者	John Wiley & Sons
収録物名	Journal of cellular and molecular medicine
巻(号)	24(8)
ページ	4589-4599
抄録	Galectin-1/LGALS1, a newly recognized angiogenic factor, contributes to the pathogenesis of diabetic retinopathy (DR). Recently, we demonstrated that glucocorticoids suppressed an interleukin-1 beta-driven inflammatory pathway for galectin-1 expression in vitro and in vivo. Here, we show glucocorticoid-mediated inhibitory mechanism against hypoxia-inducible factor (HIF)-1 alpha-involved galectin-1 expression in human Muller glial cells and the retina of diabetic mice. Hypoxia-induced increases in galectin-1/LGALS1 expression and promoter activity were attenuated by dexamethasone and triamcinolone acetonide in vitro. Glucocorticoid application to hypoxia-stimulated cells decreased HIF-1 alpha protein, but not mRNA, together with its DNA-binding activity, while transactivating TSC22 domain family member (TSC22D)3 mRNA and protein expression. Co-immunoprecipitation revealed that glucocorticoid-transactivated TSC22D3 interacted with HIF-1 alpha, leading to degradation of hypoxia-stabilized HIF-1 alpha via the ubiquitin-proteasome pathway. Silencing TSC22D3 reversed glucocorticoid-mediated ubiquitination of HIF-1 alpha and subsequent down-regulation of HIF-1 alpha and galectin-1/LGALS1 levels. Glucocorticoid treatment to mice significantly alleviated diabetes-induced retinal HIF-1 alpha and galectin-1/Lgals1 levels, while increasing TSC22D3 expression. Fibrovascular tissues from patients with proliferative DR demonstrated co-localization of galectin-1 and HIF-1 alpha in glial cells partially positive for TSC22D3. These results indicate that glucocorticoid-transactivated TSC22D3 attenuates hypoxia- and diabetes-induced retinal glial galectin-1/LGALS1 expression via HIF-1 alpha destabilization, highlighting therapeutic implications for DR in the era of anti-vascular endothelial growth factor treatment.
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	1582-1838
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1111/jcmm.15116