Glucocorticoids increase VE-cadherin expression and cause cytoskeletal rearrangements in murine brain endothelial cEND cells.
Recent studies have shown the influence of glucocorticoids on the expression of the tight junction protein occludin in the brain capillary endothelial cell line cEND, contributing to improvement in endothelial barrier functions. In this study, we investigated glucocorticoid effects on the expression of the adherens junction proteins VE- (vascular-endothelial) cadherin, alpha-catenin and beta-catenin as well as that of ZO-1, the plaque protein shared by both adherens and tight junctions on stimulation with dexamethasone. We were able to show a positive influence of dexamethasone administration on VE-cadherin protein levels as well as a rearrangement of VE-cadherin protein to the cytoskeleton after dexamethasone treatment. Investigation of transcriptional activation of the VE-cadherin promoter by dexamethasone, however, did not point to direct glucocorticoid-mediated VE-cadherin gene induction but rather suggested indirect steroid effects leading to increased VE-cadherin protein synthesis. Dexamethasone was further shown to induce cellular differentiation into a cobblestone cellular morphology and reinforcement of adherens junctions concomitant with the increased anchorage of VE-cadherin to the actin cytoskeleton. We thus propose that glucocorticoid effects on VE-cadherin protein synthesis and organization are important for the formation of both adherens and tight junction, and for improved barrier properties in microvascular brain endothelial cells.
Blecharz
Kinga G
KG
Department of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.
Drenckhahn
Detlev
D
Förster
Carola Y
CY
D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001921:Brain / Q000166:cytology*; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects; D000099152:Cadherin 5
D000199:Actins; D015703:Antigens, CD; D015820:Cadherins; D003907:Dexamethasone; D005938:Glucocorticoids; D000099152:Cadherin 5