| Prevention of murine experimental corneal trauma by epigenetic events regulating claudin 6 and claudin 9. | |
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MedLine Citation:
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PMID: 18661270 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: To study the effects of epigenetic events on corneal barrier functions, we examined tight junctions (TJs), the most important factor in the barrier function of the cornea, by using in vitro and in vivo corneal trauma models. METHODS: We examined alteration of TJ-associated gene expression and corneal barrier function in human corneal cells by methylating and demethylating promoter cytosine (CpG) islands, with and without epigenetic regulators such as trichostatin A, (TSA), 5-azacytidine (5-aza), and dimethyl sulfoxide (DMSO). We also investigated the clinical relevance of epigenetic regulators by applying these agents to murine experimental corneal trauma. RESULTS: Treatment with epigenetic regulators such as TSA, 5-aza, and DMSO significantly enhanced the expression of TJ-associated genes such as claudin 6 and claudin 9 in corneal cells, changing transcriptional signals by demethylating CpG islands. In addition, the epigenetic regulators increased transendothelial electrical resistance and suppressed fluxes of corneal cells, thus enhancing the corneal barrier function. These epigenetic regulators mediated TJ-associated gene enhancement, and the corneal barrier function enhancement was sufficient to limit the corneal fluxes in murine experimental corneal trauma. CONCLUSIONS: Epigenetic regulators enhance corneal barrier impairment by modulating TJs, so epigenetic regulation is a possible therapeutic method for corneal trauma. |
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Authors:
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Nami Nishikiori; Norimasa Sawada; Hiroshi Ohguro |
Publication Detail:
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Type: Journal Article Date: 2008-07-27 |
Journal Detail:
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Title: Japanese journal of ophthalmology Volume: 52 ISSN: 0021-5155 ISO Abbreviation: Jpn. J. Ophthalmol. Publication Date: 2008 May-Jun |
Date Detail:
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Created Date: 2008-07-28 Completed Date: 2008-11-10 Revised Date: 2011-11-23 |
Medline Journal Info:
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Nlm Unique ID: 0044652 Medline TA: Jpn J Ophthalmol Country: Japan |
Other Details:
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Languages: eng Pagination: 195-203 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Azacitidine / pharmacology Biological Transport / physiology Cornea / radiation effects* CpG Islands / genetics DNA Methylation Dimethyl Sulfoxide / pharmacology Electric Impedance Epigenesis, Genetic* Gene Expression Regulation / drug effects Humans Hydroxamic Acids / pharmacology Male Membrane Proteins / genetics* Mice Mice, Inbred C57BL Phosphoproteins RNA, Messenger / metabolism RNA, Small Interfering / pharmacology Radiation Injuries, Experimental / genetics, prevention & control* Reverse Transcriptase Polymerase Chain Reaction Tight Junctions / genetics Transfection Ultraviolet Rays |
| Chemical | |
Reg. No./Substance:
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0/Cldn9 protein, mouse; 0/Hydroxamic Acids; 0/Membrane Proteins; 0/Phosphoproteins; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/claudin 6; 0/occludin; 0/zonula occludens-1 protein; 320-67-2/Azacitidine; 58880-19-6/trichostatin A; 67-68-5/Dimethyl Sulfoxide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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