Review article: selective histone deacetylase isoforms as potential therapeutic targets in inflammatory bowel diseases - PubMed (original) (raw)

Review

doi: 10.1111/apt.13008. Epub 2014 Nov 4.

Affiliations

• PMID: 25367825
• DOI: 10.1111/apt.13008

Review

Review article: selective histone deacetylase isoforms as potential therapeutic targets in inflammatory bowel diseases

C Felice et al. Aliment Pharmacol Ther. 2015 Jan.

Abstract

Background: A link between histone deacetylases (HDACs) and intestinal inflammation has been established. HDAC inhibitors that target gut-selective inflammatory pathways represent a potential new therapeutic strategy in patients with refractory inflammatory bowel diseases (IBD).

Aims: To review the use of selective HDAC inhibitors to treat gut inflammation and to highlight potential improvements in selectivity/sensitivity by additional targeting of HDAC-regulating microRNAs (miRNAs).

Methods: Original articles and reviews have been identified using PubMed search terms: 'histone deacetylase', 'HDAC inhibitor', 'inflammatory bowel disease', 'gut inflammation,' and 'microRNA and HDAC'.

Results: The use of butyrate in distal colitis provided the first evidence that inhibition of HDACs decreases intestinal inflammation in IBD. HDAC inhibitors, such as valproic acid, vorinostat and givinostat, reduce inflammation and tissue damage in experimental murine colitis. Potential mechanisms of action for HDAC inhibitors include increased apoptosis, reduction of pro-inflammatory cytokine release, regulation of transcription factors and modulation of HDAC-regulatory miRNAs. HDAC2, HDAC3, HDAC6, HDAC9 and HDAC10 isoforms seem to be specifically involved in chronic intestinal inflammation, justifying the use of selective inhibitors as new therapeutic strategies in IBD. Controlling miRNAs for these isoforms can be identified.

Conclusions: The pro-inflammatory influence of HDACs in the gut has been confirmed, but mostly in murine studies. Considerably more human data are required to permit development of selective HDAC inhibitors for IBD treatment. Inhibition of key HDAC isoforms in combination with modulation of HDAC-regulatory miRNAs has potential as a novel therapeutic approach.

© 2014 John Wiley & Sons Ltd.

PubMed Disclaimer

Similar articles

• Histone deacetylase inhibitors and their potential role in inflammatory bowel diseases.
  Edwards AJ, Pender SL. Edwards AJ, et al. Biochem Soc Trans. 2011 Aug;39(4):1092-5. doi: 10.1042/BST0391092. Biochem Soc Trans. 2011. PMID: 21787354
• Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors.
  Khan N, Jeffers M, Kumar S, Hackett C, Boldog F, Khramtsov N, Qian X, Mills E, Berghs SC, Carey N, Finn PW, Collins LS, Tumber A, Ritchie JW, Jensen PB, Lichenstein HS, Sehested M. Khan N, et al. Biochem J. 2008 Jan 15;409(2):581-9. doi: 10.1042/BJ20070779. Biochem J. 2008. PMID: 17868033
• Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease.
  Li G, Lin J, Zhang C, Gao H, Lu H, Gao X, Zhu R, Li Z, Li M, Liu Z. Li G, et al. Gut Microbes. 2021 Jan-Dec;13(1):1968257. doi: 10.1080/19490976.2021.1968257. Gut Microbes. 2021. PMID: 34494943 Free PMC article.
• Zinc-dependent histone deacetylases: Potential therapeutic targets for arterial hypertension.
  Kee HJ, Kim I, Jeong MH. Kee HJ, et al. Biochem Pharmacol. 2022 Aug;202:115111. doi: 10.1016/j.bcp.2022.115111. Epub 2022 May 28. Biochem Pharmacol. 2022. PMID: 35640713 Review.
• Development and therapeutic impact of HDAC6-selective inhibitors.
  Dallavalle S, Pisano C, Zunino F. Dallavalle S, et al. Biochem Pharmacol. 2012 Sep 15;84(6):756-65. doi: 10.1016/j.bcp.2012.06.014. Epub 2012 Jun 21. Biochem Pharmacol. 2012. PMID: 22728920 Review.

Cited by

• Histone deacetylase inhibitor givinostat has ameliorative effect in the colitis model.
  Dibekoğlu C, Erbaş O. Dibekoğlu C, et al. Acta Cir Bras. 2022 Jul 22;37(5):e370503. doi: 10.1590/acb370503. eCollection 2022. Acta Cir Bras. 2022. PMID: 35894303 Free PMC article.
• Selective Targeting of Epigenetic Readers and Histone Deacetylases in Autoimmune and Inflammatory Diseases: Recent Advances and Future Perspectives.
  Ghiboub M, Elfiky AMI, de Winther MPJ, Harker NR, Tough DF, de Jonge WJ. Ghiboub M, et al. J Pers Med. 2021 Apr 23;11(5):336. doi: 10.3390/jpm11050336. J Pers Med. 2021. PMID: 33922725 Free PMC article. Review.
• Histone Deacetylation Inhibitors as Modulators of Regulatory T Cells.
  von Knethen A, Heinicke U, Weigert A, Zacharowski K, Brüne B. von Knethen A, et al. Int J Mol Sci. 2020 Mar 29;21(7):2356. doi: 10.3390/ijms21072356. Int J Mol Sci. 2020. PMID: 32235291 Free PMC article. Review.
• Histone deacetylase inhibitors promote eNOS expression in vascular smooth muscle cells and suppress hypoxia-induced cell growth.
  Tan X, Feng L, Huang X, Yang Y, Yang C, Gao Y. Tan X, et al. J Cell Mol Med. 2017 Sep;21(9):2022-2035. doi: 10.1111/jcmm.13122. Epub 2017 Mar 7. J Cell Mol Med. 2017. PMID: 28266122 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Ovid Technologies, Inc.

• Other Literature Sources

  • The Lens - Patent Citations Database
  • scite Smart Citations

• Molecular Biology Databases

  • Guide to Pharmacology