Claudin-5 as a novel estrogen target in vascular endothelium.
OBJECTIVE
Estrogens have multiple effects on vascular physiology and function. In the present study, we look for direct estrogen target genes within junctional proteins.


RESULTS
We use murine endothelial cell lines of brain and heart origin, which express both subtypes of estrogen receptor, ERalpha and ERbeta. Treatment of these cells with 17beta-estradiol (E2) led to an increase in transendothelial electric resistance and a most prominent upregulation of the tight junction protein claudin-5 expression. A significant increase of claudin-5 promoter activity, mRNA, and protein levels was detected in cells from both vascular beds. In protein lysates and in immunoreactions on brain sections from ovariectomized E2-treated mice, we noticed an increase in claudin-5 protein and mRNA content. Treatment of cells with a specific ERbeta agonist, diarylpropionitrile, revealed the same effect as E2 stimulation. Moreover, we detected significantly lower claudin-5 mRNA and protein content in ERbeta knockout mice.


CONCLUSIONS
We describe claudin-5 as a novel estrogen target in vascular endothelium and show in vivo (brain endothelium) and in vitro (brain and heart endothelium) effects of estrogen on claudin-5 levels. The estrogen-induced increase in junctional protein levels may lead to an improvement in vascular structural integrity and barrier function of vascular endothelium.
Burek
Malgorzata
M
Department of Anaesthesia and Critical Care, Institute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany. Burek_M@klinik.uni-wuerzburg.de
Arias-Loza
Paula A
PA
Roewer
Norbert
N
Förster
Carola Y
CY
D000818:Animals; D001921:Brain / Q000098:blood supply*; D002199:Capillary Permeability; D002460:Cell Line; D062507:Claudin-5; D003331:Coronary Vessels / Q000378:metabolism*; D017097:Electric Impedance; D042783:Endothelial Cells / Q000378:metabolism*; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D005260:Female; D015918:Infusion Pumps, Implantable; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055806:Microvessels / Q000378:metabolism; D010052:Ovariectomy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism*; D013997:Time Factors; D015533:Transcriptional Activation; D014162:Transfection; D015854:Up-Regulation
D062507:Claudin-5; C491511:Cldn5 protein, mouse; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008565:Membrane Proteins; D012333:RNA, Messenger; D004958:Estradiol