These authors contributed equally to this study.
Trichostatin A, a histone deacetylase inhibitor, suppresses proliferation and epithelial–mesenchymal transition in retinal pigment epithelium cells
Article first published online: 23 JAN 2014
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Journal of Cellular and Molecular Medicine
Volume 18, Issue 4, pages 646–655, April 2014
How to Cite
Xiao, W., Chen, X., Liu, X., Luo, L., Ye, S. and Liu, Y. (2014), Trichostatin A, a histone deacetylase inhibitor, suppresses proliferation and epithelial–mesenchymal transition in retinal pigment epithelium cells. Journal of Cellular and Molecular Medicine, 18: 646–655. doi: 10.1111/jcmm.12212
- Issue published online: 8 APR 2014
- Article first published online: 23 JAN 2014
- Manuscript Accepted: 18 NOV 2013
- Manuscript Received: 26 JUL 2013
- National Natural Science Foundation of China. Grant Number: 81270981
- Guangdong Natural Science Foundation. Grant Number: S2012020010878
- histone deacetylase inhibitor;
- epithelial–mesenchymal transition (EMT);
- retinal pigment epithelium (RPE) cells;
- proliferative vitreoretinopathy (PVR)
The proliferation and epithelial–mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells are the major pathological changes in development of proliferative vitreoretinopathy (PVR), which leads to severe visual impairment. Histone deacetylases (HDACs)-mediated epigenetic mechanisms play important roles in controlling various physiological and pathological events. However, whether HDACs are involved in the regulation of proliferation and EMT in PRE cells remains unidentified. In this study, we evaluated the expression profile of HDAC family (18 genes) and found that some of class I and class II HDACs were up-regulated in transforming growth factor-β2 (TGF-β2)/TGF-β1-stimulated RPE cells. Tricostatin A (TSA), a class I and II HDAC inhibitor, suppressed the proliferation of RPE cells by G1 phase cell cycle arrest through inhibition of cyclin/CDK/p-Rb and induction of p21 and p27. In the meantime, TSA strongly prevented TGF-β2–induced morphological changes and the up-regulation of α-SMA, collagen type I, collagen type IV, fibronectin, Snail and Slug. We also demonstrated that TSA affected not only the canonical Smad signalling pathway but also the non-canonical TGF-β/Akt, MAPK and ERK1/2 pathways. Finally, we found that the underlying mechanism of TSA affects EMT in RPE cells also through down-regulating the Jagged/Notch signalling pathway. Therefore, this study may provide a new insight into the pathogenesis of PVR, and suggests that epigenetic treatment with HDAC inhibitors may have therapeutic value in the prevention and treatment of PVR.