Abstract
Histone deacetylases (HDACs) are enzymes that balance the acetylation activities of histone acetyltransferases on chromatin remodeling and play essential roles in regulating gene transcription. In the past several years, the role of HDACs in cancer initiation and progression, as well as the therapeutic effects of HDAC inhibitors in various types of cancer, has been well studied. Recent studies indicated that HDAC activity is also associated with the development and progression of some chronic diseases characterized by fibrosis, including chronic kidney disease, cardiac hypertrophy, and idiopathic pulmonary fibrosis. Here, we review what is known about HDACs in the progression of tissue fibrosis and the potential applications of HDAC inhibitors in the treatment of disorders associated with fibroblast activation and proliferation.
Footnotes
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This work was supported by National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant DK071997].
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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ABBREVIATIONS:
- HAT
- histone acetyltransferase
- HDAC
- histone deacetylase
- CF
- cystic fibrosis
- CFTR
- cystic fibrosis transmembrane conductance regulator
- CSF-1
- colony stimulating factor-1
- ECM
- extracellular matrix
- EMT
- epithelial to mesenchymal transition
- IPF
- idiopathic pulmonary fibrosis
- NRK-49F
- rat renal interstitial fibroblasts
- NRK-52E
- rat kidney tubular epithelial cells
- NHLF
- normal human lung fibroblast
- PDGF
- platelet-derived growth factor
- PGE2
- prostaglandin E2
- PKD
- polycystic kidney disease
- SAHA
- suberoylanilide hydroxamic acid
- SK-7041
- 3-(4-substituted phenyl)-N-hydroxy-2-propenamide
- |ga-SMA
- |ga-smooth muscle actin
- STAT3
- signal transducer and activator of transcription3
- UUO
- unilateral ureteral obstruction
- SSc
- systemic sclerosis
- TGF-|gb1
- transforming growth factor-|gb1
- TSA
- trichostatin A
- 4-PBA
- sodium 4-phenylbutyrate
- LBH589
- panobinostat
- AG490
- tyrphostinAG 490 [(E)-2-cyano-3-(3,4-dihydrophenyl)-N-(phenylmethyl)-2-propenamide]
- Received May 4, 2010.
- Accepted August 17, 2010.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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