HDAC Inhibitors: Therapeutic Potential in Fibrosis-Associated Human Diseases
Abstract
:1. Introduction
1.1. Fibrosis
1.2. HDAC and HDAC Inhibitors
1.3. Functional Relevance of HDAC in Fibrogenesis
1.4. HDAC Inhibitors and Their Therapeutic Potential
2. Experimental Outcomes of HDAC Inhibitors in Animal Models of Fibrosis-Associated Disease
2.1. Liver Cirrhosis
2.2. Cardiac Fibrosis
2.3. Pulmonary Fibrosis
2.4. Renal Fibrosis
2.5. Miscellaneous Diseases
3. Limitations and Future Perspectives
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AF | Atrial fibrillation |
BDL | Bile duct ligation |
CFTR | Cystic fibrosis transmembrane conductance regulator |
HAT | Histone acetyltransferase |
HDAC | Histone deacetylase |
HDACI | Histone deacetylase inhibitor |
HSC | Hepatic stellate cells |
IPF | Idiopathic pulmonary fibrosis |
NHLF | Normal human lung fibroblast |
PKD | Polycystic kidney disease |
PTCL | Percutaneous T cell lymphoma |
STAT | Signal transducer and activator of transcription |
STZ | Streptozotocin |
TGF-β | Transforming growth factor β |
TNF-α | Tumor necrosis factor α |
TSA | Trichostatin A |
UUO | Unilateral ureteral obstruction |
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HDAC Inhibitor | Selectivity | Model | Output (Except Fibrosis) | Reference | |
---|---|---|---|---|---|
Liver cirrhosis | SAHA HNHA | pan pan | Bile duct ligation | Improved hepatic function Survival ↑ | [37] |
MC1568 | HDAC4/5/6 | CCl4 | HSC activation ↓ | [38] | |
Valproate | pan | thioacetamide | HSC activation ↓ | [39] | |
Cardiac fibrosis | TSA SK7041 | pan class I | Pressure overload | Heart failure ↓ Cardiac hypertrophy ↓ | [40] |
Api-D | class I | Pressure overload | Heart failure ↓ Cardiac hypertrophy ↓ | [41] | |
TSA Scriptaid | pan pan | Pressure overload | Heart failure ↓ Cardiac hypertrophy ↓ | [42] | |
Valproate | pan | Pressure overload MCT | RV hypertrophy | [43] | |
TSA | pan | TgHopX | Cx40 ↑ Normalized conduction | [44] | |
Tacedinaline | class I | TgHopX pacing (dog) | Atrial fibrillation ↓ Immune cell infiltration ↓ | [45] | |
Lung fibrosis | TSA | pan | TGF-β (NHLF cell) | Myofibroblast differentiation ↓ | [25] |
SAHA | pan | Bleomycin | Lung compliance ↑ Airway resistance ↓ | [46] | |
SAHA panobinostat | pan pan | Primary cells from IPF patient | Correction of epigenetic abnormality | [47] | |
Renal fibrosis | TSA | pan | UUO | Immune cell infiltration ↓ | [48] |
TSA | pan | UUO | Tubular cell apoptosis ↓ | [49] | |
Valproate | pan | UUO | Macrophage infiltration ↓ | [50] | |
CG200745 | pan | UUO | Serum NGAL level ↓ | [51] | |
TSA Valproate SK7041 | pan pan class I | STZ | Urine protein/Cr ↓ EMT ↓ | [52] |
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Yoon, S.; Kang, G.; Eom, G.H. HDAC Inhibitors: Therapeutic Potential in Fibrosis-Associated Human Diseases. Int. J. Mol. Sci. 2019, 20, 1329. https://doi.org/10.3390/ijms20061329
Yoon S, Kang G, Eom GH. HDAC Inhibitors: Therapeutic Potential in Fibrosis-Associated Human Diseases. International Journal of Molecular Sciences. 2019; 20(6):1329. https://doi.org/10.3390/ijms20061329
Chicago/Turabian StyleYoon, Somy, Gaeun Kang, and Gwang Hyeon Eom. 2019. "HDAC Inhibitors: Therapeutic Potential in Fibrosis-Associated Human Diseases" International Journal of Molecular Sciences 20, no. 6: 1329. https://doi.org/10.3390/ijms20061329