ArticleMolecular vision2008
Histone deacetylase inhibitors blocked activation and caused senescence of corneal stromal cells.
Article in Molecular vision, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The trial behind it
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- CRISPR-based screening identifies XPO7 as a positive regulator of senescence.Protein & cell · 2023Article
- Unravelling the Impact of Cyclic Mechanical Stretch in Keratoconus-A Transcriptomic Profiling Study.International journal of molecular sciences · 2023Article
- Review
- Topical onion juice mitigates the morphological alterations of the cornea in the aged male rats.Anatomy & cell biology · 2021Article
- Multi-level consistent changes of the ECM pathway identified in a typical keratoconus twin's family by multi-omics analysis.Orphanet journal of rare diseases · 2020Article
- Inhibition of Human Corneal Myofibroblast Formation.Investigative ophthalmology & visual science · 2018Article
- Suppression of fibrosis in human pterygium fibroblasts by butyrate and phenylbutyrate.International journal of ophthalmology · 2017Article
- Transcriptome Analysis of Cultured Limbal Epithelial Cells on an Intact Amniotic Membrane following Hypothermic Storage in Optisol-GS.Journal of functional biomaterials · 2016Article
- Decreased Integrity, Content, and Increased Transcript Level of Mitochondrial DNA Are Associated with Keratoconus.PloS one · 2016Article
- Association of histone acetylation at the ACTA2 promoter region with epithelial mesenchymal transition of lens epithelial cells.Eye (London, England) · 2015Article
- Effect of HDAC Inhibitors on Corneal Keratocyte Mechanical Phenotypes in 3-D Collagen Matrices.Molecular vision · 2015Article
- The role of epigenetics in the fibrotic processes associated with glaucoma.Journal of ophthalmology · 2014Review
- Characterization of the regulation and function of zinc-dependent histone deacetylases during rodent liver regeneration.Hepatology (Baltimore, Md.) · 2013Article
- Role of histone deacetylase 2 in epigenetics and cellular senescence: implications in lung inflammaging and COPD.American journal of physiology. Lung cellular and molecular physiology · 2012Review
- Combined treatment with antioxidants and immunosuppressants on cytokine release by human peripheral blood mononuclear cells - chemically injured keratocyte reaction.Molecular vision · 2011Article
- Targeting the epigenome: effects of epigenetic treatment strategies on genomic stability in healthy human cells.Clinical epigenetics · 2010Article
- Effect of EGF-induced HDAC6 activation on corneal epithelial wound healing.Investigative ophthalmology & visual science · 2010Article
- Immunomodulatory effects of deacetylase inhibitors: therapeutic targeting of FOXP3+ regulatory T cells.Nature reviews. Drug discovery · 2009Review
- Trichostatin A Restores Expression of Adherens and Tight Junction Proteins during Transforming Growth Factor β-Mediated Epithelial-to-Mesenchymal Transition.Journal of ophthalmic & vision researchArticle
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCorneal myofibroblasts differentiated from activated corneal stromal cells are the major cellular sources of extracellular matrix synthesis for the repair of corneal injury. In this study, the effects of histone deacetylase (HDAC) inhibitors on the activation, proliferation, migration and senescence of corneal stromal cells were evaluated.
methodsPrimary human and mouse corneal stromal cells were harvested by sequential digestion with dispase and collagenase, and cultured in DMEM/F-12 media under serum-free (keratocytes), serum- (corneal fibroblasts) and TGFbeta1-supplemented (corneal myofibroblasts) conditions. The responses of corneal stromal cells to HDAC inhibitors were characterized by cDNA microarray, real time PCR, immunocytochemistry and western blot analysis. The effects of HDAC inhibitors on corneal fibroblast proliferation, cell cycle distribution, migration and senescence were also assessed in vitro.
resultsFetal bovine serum and TGFbeta1 activated the transdifferentiation of corneal stromal cells into fibroblasts and myofibroblasts, indicated by cell spreading, renewed assembly of actin filaments and enhanced expression of extracellular matrix components, all of which were suppressed by the addition of HDAC inhibitors. HDAC inhibitors inhibited the proliferation of corneal fibroblasts by decreasing the proportion in the S-phase and increasing the proportion in the G0/G1 and G2/M cell cycle checkpoints. HDAC inhibitors showed a dose-dependent inhibitory effects on the migration of corneal fibroblasts. In addition, HDAC inhibitors induced the senescence of corneal myofibroblasts as shown by enhanced staining of beta-galactosidase and upregulated expression of p16(ink4a).
conclusionsHDAC inhibitors may affect corneal stromal cells by inhibiting myofibroblastic differentiation, cell proliferation, migration and by inducing cell senescence. Thus, this has implications for future studies in the development of promising drugs in the prevention or treatment of corneal haze and scar formation.
Indexed as
Identifiers
19122829PMC2613076W2099762491What OpenQuestion holds
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.