Involvement of Muller Glial Autoinduction of TGF-beta in Diabetic Fibrovascular Proliferation Via Glial-Mesenchymal Transition

Wu, Di; Kanda, Atsuhiro; Liu, Ye; Noda, Kousuke; Murata, Miyuki; Ishida, Susumu

Involvement of Muller Glial Autoinduction of TGF-beta in Diabetic Fibrovascular Proliferation Via Glial-Mesenchymal Transition

Wu, Di; Kanda, Atsuhiro; Liu, Ye et al.

Investigative ophthalmology & visual science, 2020, 61(14), 29

Permalink : https://hdl.handle.net/2115/80433

このアイテムのアクセス数:652件（2026-10-09 21:06 集計）

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https://doi.org/10.1167/iovs.61.14.29			30

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アクセス権	open access
URI	https://hdl.handle.net/2115/80433
タイトル	Involvement of Muller Glial Autoinduction of TGF-beta in Diabetic Fibrovascular Proliferation Via Glial-Mesenchymal Transition
著者	Wu, Di ; Kanda, Atsuhiro ; Liu, Ye ; Noda, Kousuke ; Murata, Miyuki ; Ishida, Susumu
著者名 Wu, Di
e-Rad_Researcher 80342707 著者名 Kanda, Atsuhiro
著者名 Liu, Ye
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
	fibrovascular proliferation
	Muller glial-mesenchymal transition
	transforming growth factor-beta vascular endothelial growth factor-A
発行日	2020-12
出版者	Association for Research in Vision and Ophthalmology（ARVO）
収録物名	Investigative ophthalmology & visual science
巻(号)	61(14)
ページ	29
抄録	PURPOSE. Muller glial-mesenchymal transition (GMT) is reported as the fibrogenic mechanism promoted by TGF-beta-SNAIL axis in Muller cells transdifferentiated into myofibroblasts. Here we show the multifaceted involvement of TGF-beta in diabetic fibrovascular proliferation via Muller GMT and VEGF-A production. METHODS. Surgically excised fibrovascular tissues from the eyes of patients with proliferative diabetic retinopathy were processed for immunofluorescence analyses of TGF beta downstream molecules. Human Muller glial cells were used to evaluate changes in gene and protein expression with real-time quantitative PCR and ELISA, respectively. Immunoblot analyses were performed to detect TGF-beta signal activation. RESULTS. Muller glial cells in patient fibrovascular tissues were immunopositive for GMT-related molecular markers, including SNAIL and smooth muscle protein 22, together with colocalization of VEGF-A and TGF-beta receptors. In vitro administration of TGF-beta 1/2 upregulated TGFB1 and TGFB2, both of which were suppressed by inhibitors for nuclear factor-kappa B, glycogen synthase kinase-3, and p38 mitogen-activated protein kinase. Of the various profibrotic cytokines, TGF-beta 1/2 application exclusively induced Muller glial VEGFA mRNA expression, which was decreased by pretreatment with small interfering RNA for SMAD2 and inhibitors for p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Supporting these findings, TGF-beta 1/2 stimulation to Muller cells increased the phosphorylation of these intracellular signaling molecules, all of which were also activated in Muller glial cells in patient fibrovascular tissues. CONCLUSIONS. This study underscored the significance of Muller glial autoinduction of TGF-beta as a pathogenic cue to facilitate diabetic fibrovascular proliferation via TGF-beta-driven GMT and VEGF-A-driven angiogenesis.
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-NonCommercial-NoDerivatives 4.0 International
PISSN	0146-0404
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1167/iovs.61.14.29