ArticleAmerican journal of physiology. Lung cellular and molecular physiology2019
HDAC8 inhibition ameliorates pulmonary fibrosis.
Article in American journal of physiology. Lung cellular and molecular physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 67 citations in OpenAlex.
- Expression of HDAC2 and HDAC8 in the airways of COPD patients is associated with responsiveness to ICS: insights from the HISTORIC study.The European respiratory journal · 2026Article
- HDAC8-mediated CAPZB desuccinylation enhances cytoskeleton remodeling to promote idiopathic pulmonary fibrosis.Communications biology · 2026Article
- Epigenetic regulatory mechanisms and translational applications in idiopathic pulmonary fibrosis.American journal of clinical and experimental immunology · 2026Review
- A deep generative model for deciphering cellular dynamics and in silico drug discovery in complex diseases.Nature biomedical engineering · 2025Article
- Contribution of histone deacetylases (HDACs) to the regulation of histone and non-histone proteins: implications for fibrotic diseases.BMB reports · 2025Review
- Mechanisms and Therapeutic Potential of Myofibroblast Transformation in Pulmonary Fibrosis.Journal of respiratory biology and translational medicine · 2025Article
- Article
- Arylcarboxamide Derivatives as Promising HDAC8 Inhibitors: An Overview in Light of Structure-activity Relationship and Binding Mode of Interaction Analysis.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Review
- Histone Deacetylase (HDAC) Inhibitors as a Novel Therapeutic Option Against Fibrotic and Inflammatory Diseases.Biomolecules · 2024Review
- HDAC8 Enhances the Function of HIF-2α by Deacetylating ETS1 to Decrease the Sensitivity of TKIs in ccRCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Fibroblast and myofibroblast activation in normal tissue repair and fibrosis.Nature reviews. Molecular cell biology · 2024Review
- Modelling and targeting mechanical forces in organ fibrosis.Nature reviews bioengineering · 2024Article
- Epigenetic regulation of pulmonary inflammation.Seminars in cell & developmental biology · 2024Review
- The evolution ofEuropean respiratory review : an official journal of the European Respiratory Society · 2024Review
- Histone deacetylases: potential therapeutic targets for idiopathic pulmonary fibrosis.Frontiers in cell and developmental biology · 2024Review
- Curcumin and PCI-34051 combined treatment ameliorates inflammation and fibrosis by affecting MAP kinase pathway.Inflammopharmacology · 2023Article
- Epigenetic perspectives associated with COVID-19 infection and related cytokine storm: an updated review.Infection · 2023Review
- COPD Patients Exhibit Distinct Gene Expression, Accelerated Cellular Aging, and Bias to M2 Macrophages.International journal of molecular sciences · 2023Article
- Epigenetics as a versatile regulator of fibrosis.Journal of translational medicine · 2023Review
- Pathological Role of HDAC8: Cancer and Beyond.Cells · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative lung disease, and fibroblast-myofibroblast differentiation (FMD) is thought to be a key event in the pathogenesis of IPF. Histone deacetylase-8 (HDAC8) has been shown to associate with α-smooth muscle actin (α-SMA; a marker of FMD) and regulates cell contractility in vascular smooth muscle cells. However, the role of HDAC8 in FMD or pulmonary fibrosis has never been reported. This study investigated the role of HDAC8 in pulmonary fibrosis with a focus on FMD. We observed that HDAC8 expression was increased in IPF lung tissue as well as transforming growth factor (TGF)β1-treated normal human lung fibroblasts (NHLFs). Immunoprecipitation experiments revealed that HDAC8 was associated with α-SMA in TGFβ1-treated NHLFs. HDAC8 inhibition with NCC170 (HDAC8-selective inhibitor) repressed TGFβ1-induced fibroblast contraction and α-SMA protein expression in NHLFs cultured in collagen gels. HDAC8 inhibition with HDAC8 siRNA also repressed TGFβ1-induced expression of profibrotic molecules such as fibronectin and increased expression of antifibrotic molecules such as peroxisome proliferator-activated receptor-γ (PPARγ). Chromatin immunoprecipitation quantitative PCR using an antibody against H3K27ac (histone H3 acetylated at lysine 27; a known HDAC8 substrate and a marker for active enhancers) suggested that HDAC8 inhibition with NCC170 ameliorated TGFβ1-induced loss of H3K27ac at the PPARγ gene enhancer. Furthermore, NCC170 treatment significantly decreased fibrosis measured by Ashcroft score as well as expression of type 1 collagen and fibronectin in bleomycin-treated mouse lungs. These data suggest that HDAC8 contributes to pulmonary fibrosis and that there is a therapeutic potential for HDAC8 inhibitors to treat IPF as well as other fibrotic lung diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.