ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Histone deacetylase inhibitors prevent pulmonary endothelial hyperpermeability and acute lung injury by regulating heat shock protein 90 function.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 43 citations in OpenAlex.
- DRD1 downregulation contributes to mechanical stretch-induced lung endothelial barrier dysfunction.Theranostics · 2021Trial
- Macrophage reprogramming and functional plasticity in sepsis.Frontiers in immunology · 2026Review
- HDAC7 promotes cardiomyocyte proliferation by suppressing myocyte enhancer factor 2.Journal of molecular cell biology · 2025Article
- The Role of HDAC3 in Pulmonary Diseases.Lung · 2025Review
- Epigenetic mechanisms mediate cytochrome P450 1A1 expression and lung endothelial injury caused by MRSA in vitro and in vivo.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Histone deacetylases: Regulation of vascular homeostasis via endothelial cells and vascular smooth muscle cells and the role in vascular pathogenesis.Genes & diseases · 2024Review
- Epigenetic regulation of pulmonary inflammation.Seminars in cell & developmental biology · 2024Review
- Zinc-Dependent Histone Deacetylases in Lung Endothelial Pathobiology.Biomolecules · 2024Review
- Bu-Shen-Tian-Jing formulas alleviate the mitochondrial damage induced by oxidative stress in ovarian granulosa cells exposed to DEHP through the HDAC3-HSP90AA pathway.Pharmaceutical biology · 2023Article
- Male histone deacetylase 6 (HDAC6) knockout mice have enhanced ventilatory responses to hypoxic challenge.Frontiers in physiology · 2023Article
- Qi-Dong-Huo-Xue-Yin balances the immune microenvironment to protect against LPS induced acute lung injury.Frontiers in pharmacology · 2023Article
- Suberoylanilide hydroxamic acid suppresses axonal damage and neurological dysfunction after subarachnoid hemorrhage via the HDAC1/HSP70/TDP-43 axis.Experimental & molecular medicine · 2022Article
- NF-κB-dependent repression of Sox18 transcription factor requires the epigenetic regulators histone deacetylases 1 and 2 in acute lung injury.Frontiers in physiology · 2022Article
- Identification of early and intermediate biomarkers for ARDS mortality by multi-omic approaches.Scientific reports · 2021Observational
- The critical roles of histone deacetylase 3 in the pathogenesis of solid organ injury.Cell death & disease · 2021Review
- Role of HDAC6 inhibition in sepsis-induced acute respiratory distress syndrome (Review).Experimental and therapeutic medicine · 2021Review
- Inhibition of Class IIa HDACs improves endothelial barrier function in endotoxin-induced acute lung injury.Journal of cellular physiology · 2021Article
- Molecular Mechanisms of Vascular Damage During Lung Injury.Advances in experimental medicine and biology · 2021Review
- Microtubules as Major Regulators of Endothelial Function: Implication for Lung Injury.Frontiers in physiology · 2021Review
- P53 in the impaired lungs.DNA repair · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Transendothelial hyperpermeability caused by numerous agonists is dependent on heat shock protein 90 (Hsp90) and leads to endothelial barrier dysfunction (EBD). Inhibition of Hsp90 protects and restores transendothelial permeability. Hyperacetylation of Hsp90, as by inhibitors of histone deacetylase (HDAC), suppresses its chaperone function and mimics the effects of Hsp90 inhibitors. In this study we assessed the role of HDAC in mediating lipopolysaccharide (LPS)-induced transendothelial hyperpermeability and acute lung injury (ALI). We demonstrate that HDAC inhibition protects against LPS-mediated EBD. Inhibition of multiple HDAC by the general inhibitors panobinostat or trichostatin provided protection against LPS-induced transendothelial hyperpermeability, acetylated and suppressed Hsp90 chaperone function, and attenuated RhoA activity and signaling crucial to endothelial barrier function. Treatment with the HDAC3-selective inhibitor RGFP-966 or the HDAC6-selective inhibitor tubastatin A provided partial protection against LPS-mediated transendothelial hyperpermeability. Similarly, knock down of HDAC3 and HDAC6 by specific small-interfering RNAs provided significant protection against LPS-induced EBD. Furthermore, combined pharmacological inhibition of both HDAC3 and -6 attenuated the inflammation, capillary permeability, and structural abnormalities associated with LPS-induced ALI in mice. Together these data indicate that HDAC mediate increased transendothelial hyperpermeability caused by LPS and that inhibition of HDAC protects against LPS-mediated EBD and ALI by suppressing Hsp90-dependent RhoA activity and signaling.
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