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Article: Dexamethasone disrupts intercellular junction formation and cytoskeleton organization in human trabecular meshwork cells

TitleDexamethasone disrupts intercellular junction formation and cytoskeleton organization in human trabecular meshwork cells
Authors
Issue Date2010
PublisherMolecular Vision. The Journal's web site is located at http://www.molvis.org/molvis/
Citation
Molecular Vision, 2010, v. 16, p. 61-71 How to Cite?
AbstractPurpose: Patients reproduce symptoms of primary open-angle glaucoma (POAG) when treated with glucocorticoids (GCs) topically on the eyes. Here we investigated the effects of GCs on junctional protein expression and cytoskeleton organization in primary human trabecular meshwork (TM) cultures to understand the molecular pathologies of POAG. Methods: Human TM cells from POAG (GTM) and age-matched nondiseased (NTM) individuals were obtained by standard surgical trabeculectomy. Some of the cultures were treated with dexamethasone (DEX), a synthetic GC, at 1-5×10-7 mol/l for 1-7 days. The expression levels of zonula occluden-1 (ZO-1) and connexin43 (Cx43) in TM cells with or without DEX treatment were measured using reverse transcription (RT)-PCR, immunocytochemistry, and western blot analysis. Results: mRNA and proteins of ZO-1 and Cx43 were found in both NTM and GTM cells. ZO-1 and Cx43 were located on the plasma membrane, especially along the border of adjacent cells. ZO-1 had no marked changes in localization in NTM and GTM cells after treatment with 10-7 mol/l DEX for 48 h, whereas Cx43 appeared to increase in the cytoplasm. mRNA of two ZO-1 isoforms, α+ and α-, were present in TM cells, and the former was expressed less than the latter. Only ZO-1 α- isoform protein was expressed in NTM cells, whereas proteins of both isoforms were found in GTM cells. DEX increased the protein levels of ZO-1 and Cx43 in both NTM and GTM cells. DEX also altered the F-actin architecture and promoted cross-linked actin network formation, the effects of which were more pronounced in GTM cells. Conclusions: Our findings not only provide molecular insights to the pathogenesis of GC-induced glaucoma but also suggest that junctional proteins ZO-1 and Cx43 as well as F-actin are targets for developing new modalities in glaucoma therapy. © 2010 Molecular Vision.
Persistent Identifierhttp://hdl.handle.net/10722/169857
ISSN
2015 Impact Factor: 2.11
2015 SCImago Journal Rankings: 1.037
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhuo, YHen_HK
dc.contributor.authorHe, Yen_HK
dc.contributor.authorLeung, KWen_HK
dc.contributor.authorHou, Fen_HK
dc.contributor.authorLi, YQen_HK
dc.contributor.authorChai, Fen_HK
dc.contributor.authorGe, Jen_HK
dc.date.accessioned2012-10-25T04:57:07Z-
dc.date.available2012-10-25T04:57:07Z-
dc.date.issued2010en_HK
dc.identifier.citationMolecular Vision, 2010, v. 16, p. 61-71en_HK
dc.identifier.issn1090-0535en_HK
dc.identifier.urihttp://hdl.handle.net/10722/169857-
dc.description.abstractPurpose: Patients reproduce symptoms of primary open-angle glaucoma (POAG) when treated with glucocorticoids (GCs) topically on the eyes. Here we investigated the effects of GCs on junctional protein expression and cytoskeleton organization in primary human trabecular meshwork (TM) cultures to understand the molecular pathologies of POAG. Methods: Human TM cells from POAG (GTM) and age-matched nondiseased (NTM) individuals were obtained by standard surgical trabeculectomy. Some of the cultures were treated with dexamethasone (DEX), a synthetic GC, at 1-5×10-7 mol/l for 1-7 days. The expression levels of zonula occluden-1 (ZO-1) and connexin43 (Cx43) in TM cells with or without DEX treatment were measured using reverse transcription (RT)-PCR, immunocytochemistry, and western blot analysis. Results: mRNA and proteins of ZO-1 and Cx43 were found in both NTM and GTM cells. ZO-1 and Cx43 were located on the plasma membrane, especially along the border of adjacent cells. ZO-1 had no marked changes in localization in NTM and GTM cells after treatment with 10-7 mol/l DEX for 48 h, whereas Cx43 appeared to increase in the cytoplasm. mRNA of two ZO-1 isoforms, α+ and α-, were present in TM cells, and the former was expressed less than the latter. Only ZO-1 α- isoform protein was expressed in NTM cells, whereas proteins of both isoforms were found in GTM cells. DEX increased the protein levels of ZO-1 and Cx43 in both NTM and GTM cells. DEX also altered the F-actin architecture and promoted cross-linked actin network formation, the effects of which were more pronounced in GTM cells. Conclusions: Our findings not only provide molecular insights to the pathogenesis of GC-induced glaucoma but also suggest that junctional proteins ZO-1 and Cx43 as well as F-actin are targets for developing new modalities in glaucoma therapy. © 2010 Molecular Vision.en_HK
dc.languageengen_US
dc.publisherMolecular Vision. The Journal's web site is located at http://www.molvis.org/molvis/en_HK
dc.relation.ispartofMolecular Visionen_HK
dc.subject.meshActins - Metabolismen_US
dc.subject.meshAdolescenten_US
dc.subject.meshAdulten_US
dc.subject.meshCell Counten_US
dc.subject.meshCell Shape - Drug Effectsen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshConnexin 43 - Genetics - Metabolismen_US
dc.subject.meshCross-Linking Reagents - Pharmacologyen_US
dc.subject.meshCytoskeleton - Drug Effects - Metabolismen_US
dc.subject.meshDexamethasone - Pharmacologyen_US
dc.subject.meshGene Expression Regulation - Drug Effectsen_US
dc.subject.meshGlaucoma, Open-Angle - Metabolism - Pathologyen_US
dc.subject.meshHumansen_US
dc.subject.meshIntercellular Junctions - Drug Effects - Pathologyen_US
dc.subject.meshMaleen_US
dc.subject.meshMembrane Proteins - Genetics - Metabolismen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshPhosphoproteins - Genetics - Metabolismen_US
dc.subject.meshTrabecular Meshwork - Drug Effects - Metabolism - Pathologyen_US
dc.subject.meshYoung Adulten_US
dc.titleDexamethasone disrupts intercellular junction formation and cytoskeleton organization in human trabecular meshwork cellsen_HK
dc.typeArticleen_HK
dc.identifier.emailLeung, KW: kwleung1@hku.hken_HK
dc.identifier.authorityLeung, KW=rp01674en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid20090922en_HK
dc.identifier.scopuseid_2-s2.0-77949315555en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77949315555&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume16en_HK
dc.identifier.spage61en_HK
dc.identifier.epage71en_HK
dc.identifier.isiWOS:000275715600001-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridZhuo, YH=7005221373en_HK
dc.identifier.scopusauthoridHe, Y=7404942872en_HK
dc.identifier.scopusauthoridLeung, KW=13106059300en_HK
dc.identifier.scopusauthoridHou, F=16241218900en_HK
dc.identifier.scopusauthoridLi, YQ=35109176800en_HK
dc.identifier.scopusauthoridChai, F=35108877700en_HK
dc.identifier.scopusauthoridGe, J=25421653600en_HK

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