title: Largazole, an inhibitor of class I histone deacetylases, attenuates inflammatory corneal neovascularization.
abstract: Histone deacetylases (HDACs) regulate gene transcription by modifying the acetylation level of histone and nonhistone proteins. In this study, we examined the effect of largazole, an inhibitor of class I HDACs, on inflammatory corneal angiogenesis. In a mouse model of alkali-induced corneal neovascularization (CNV), topical application of largazole to the injured corneas attenuated CNV. In addition, in vivo treatment with largazole down-regulated the expression of the pro-angiogenic factors VEGF, b-FGF, TGFβ1 and EGF but up-regulated the expression of the anti-angiogenic factors Thrombospondin-1 (Tsp-1), Tsp-2 and ADAMTS-1 in the injured corneas. Furthermore, largazole inhibited the expression of pro-angiogenic factors, migration, proliferation and tube formation by human microvascular endothelial cells (HEMC-1) in vitro. These data indicate that largazole has therapeutic potential for angiogenesis-associated diseases.
authors: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 S Xianlie Road, Guangzhou 510060, China.
authors: Hongyan
authors: H
authors: Zhou
authors: Guangzhou Institute of Biomedicine and Health, CAS, Guangzhou 510663, China.
authors: Sheng
authors: S
authors: Jiang
authors: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 S Xianlie Road, Guangzhou 510060, China.
authors: Jianping
authors: J
authors: Chen
authors: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 S Xianlie Road, Guangzhou 510060, China.
authors: Xiangrong
authors: X
authors: Ren
authors: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 S Xianlie Road, Guangzhou 510060, China.
authors: Jiayi
authors: J
authors: Jin
authors: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 S Xianlie Road, Guangzhou 510060, China. Electronic address: sushaobo7836@gmail.com.
authors: Shao Bo
authors: SB
authors: Su
mesh_terms: D051722:ADAM Proteins / Q000235:genetics; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D047630:Depsipeptides / Q000494:pharmacology / Q000627:therapeutic use*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004815:Epidermal Growth Factor / Q000235:genetics; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D019700:Thrombospondin 1 / Q000235:genetics; D019699:Thrombospondins / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D000099262:Thrombospondin 2
chemical_list: D051722:ADAM Proteins; D000893:Anti-Inflammatory Agents; D047630:Depsipeptides; D004815:Epidermal Growth Factor; D005346:Fibroblast Growth Factors; D056572:Histone Deacetylase Inhibitors; D012333:RNA, Messenger; D013844:Thiazoles; D019700:Thrombospondin 1; D019699:Thrombospondins; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D000099262:Thrombospondin 2; C527895:largazole
keywords: Angiogenesis; CNV; HDACs; Largazole