TY - JOUR
T1 - Suberoylanilide hydroxamic acid suppresses inflammation-induced neovascularization
AU - Zhou, Hongyan
AU - Jiang, Sheng
AU - Chen, Jianping
AU - Su, Shao Bo
N1 - Publisher Copyright:
© 2014, National Research Council of Canada. All rights reserved.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - Histone deacetylases (HDACs) regulate gene transcription by modifying the acetylation of histone and nonhistone proteins. Deregulated expression of HDACs has been implicated in tumorigenesis and angiogenesis. In this study, we examined the effect of suberoylanilide hydroxamic acid (SAHA), a potent inhibitor of HDACs, on inflammatory corneal angiogenesis. In a mouse model of alkali-induced corneal neovascularization (CNV), topical application of SAHA to the injured corneas attenuated CNV. In addition, in vivo treatment with SAHA downregulated the expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor beta 1 (TGFβ1), and epidermal growth factor (EGF), but upregulated the expression of the anti-angiogenic factors thrombospondin (TSP)-1, TSP-2, and ADAMTS-1 in the injured corneas. Furthermore, SAHA 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 SAHA has therapeutic potential for CNV.
AB - Histone deacetylases (HDACs) regulate gene transcription by modifying the acetylation of histone and nonhistone proteins. Deregulated expression of HDACs has been implicated in tumorigenesis and angiogenesis. In this study, we examined the effect of suberoylanilide hydroxamic acid (SAHA), a potent inhibitor of HDACs, on inflammatory corneal angiogenesis. In a mouse model of alkali-induced corneal neovascularization (CNV), topical application of SAHA to the injured corneas attenuated CNV. In addition, in vivo treatment with SAHA downregulated the expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor beta 1 (TGFβ1), and epidermal growth factor (EGF), but upregulated the expression of the anti-angiogenic factors thrombospondin (TSP)-1, TSP-2, and ADAMTS-1 in the injured corneas. Furthermore, SAHA 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 SAHA has therapeutic potential for CNV.
KW - Angiogenesis
KW - CNV
KW - HDACs
KW - SAHA
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U2 - 10.1139/cjpp-2014-0117
DO - 10.1139/cjpp-2014-0117
M3 - Article
C2 - 25272091
AN - SCOPUS:84907556201
VL - 92
SP - 879
EP - 885
JO - Canadian Journal of Physiology and Pharmacology
JF - Canadian Journal of Physiology and Pharmacology
SN - 0008-4212
IS - 10
ER -