Largazole, an inhibitor of class i histone deacetylases, attenuates inflammatory corneal neovascularization

Hongyan Zhou, Sheng Jiang, Jianping Chen, Xiangrong Ren, Jiayi Jin, Shao Bo Su

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)619-626
Number of pages8
JournalEuropean Journal of Pharmacology
Volume740
DOIs
StatePublished - Oct 5 2014
Externally publishedYes

Keywords

  • Angiogenesis
  • CNV
  • HDACs
  • Largazole

ASJC Scopus subject areas

  • Pharmacology

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