TY - JOUR
T1 - Largazole, an inhibitor of class i histone deacetylases, attenuates inflammatory corneal neovascularization
AU - Zhou, Hongyan
AU - Jiang, Sheng
AU - Chen, Jianping
AU - Ren, Xiangrong
AU - Jin, Jiayi
AU - Su, Shao Bo
N1 - Funding Information:
This project was supported in part by the grants from Guangdong Natural Science Foundation ( S2011010006048 ) and the Fundamental Research Funds of State Key Laboratory of Ophthalmology ( 303060202400439 ).
Publisher Copyright:
© 2014 Elsevier B.V. All rights reserved.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2014/10/5
Y1 - 2014/10/5
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - CNV
KW - HDACs
KW - Largazole
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U2 - 10.1016/j.ejphar.2014.06.019
DO - 10.1016/j.ejphar.2014.06.019
M3 - Article
C2 - 24973692
AN - SCOPUS:84919448332
SN - 0014-2999
VL - 740
SP - 619
EP - 626
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -