title: Claudin domain containing 1 contributing to endothelial cell adhesion decreases in presence of cerebellar hemorrhage.
abstract: The claudin family comprises four-pass transmembrane proteins involved in the formation of tight junctions (TJs). Relatively recently, claudin domain containing (CLDND) 1, also known as claudin-25, was identified as a novel member of the claudin family. In the present study, we revealed that in the adult murine brain, CLDND1 is abundant in the cerebellum among common sites of intracerebral hemorrhage. Thus, the dynamics of CLDND1 after cerebellar hemorrhage were examined. Both CLDND1 mRNA and protein levels transiently decreased at 24 hr after hemorrhagic insult. For immunostaining, an anti-CLDND1 antibody that recognizes the specific epitope in the extracellular first loop was prepared. Dual immunohistochemical staining with CD31 using coronal cryosections of intact murine cerebellum tissue revealed that CLDND1 is expressed on endothelial cells. We therefore performed an in vitro permeability test using a human brain endothelial cell (HBEC) line to reveal whether CLDND1 contributes to cell adhesion like other claudins. CLDND1 was expressed on HBECs as well as in murine cerebellum tissue, and a strong signal was observed at TJs. RNA interference against CLDND1 decreased both the mRNA and protein levels without cytotoxicity. The permeability to small molecules, but not to large ones, across confluent HBECs increased on CLDND1 knockdown compared with mock-treated cells. These results suggest that the transient decrease of CLDND1 after cerebellar hemorrhage is responsible for low-molecular-weight selective vascular hyperpermeability. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Pharmacotherapeutics, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Higashimura-cho, Fukuyama, Hiroshima, Japan.
authors.forename: Masatoshi
authors.identifier: 0000-0001-9832-0990
authors.initials: M
authors.lastname: Ohnishi
authors.affiliation: Department of Pharmacotherapeutics, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Higashimura-cho, Fukuyama, Hiroshima, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ochiai
authors.affiliation: Department of Pharmacotherapeutics, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Higashimura-cho, Fukuyama, Hiroshima, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Matsuoka
authors.affiliation: Department of Pharmacotherapeutics, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Higashimura-cho, Fukuyama, Hiroshima, Japan.
authors.forename: Marina
authors.initials: M
authors.lastname: Akagi
authors.affiliation: Department of Pharmacotherapeutics, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Higashimura-cho, Fukuyama, Hiroshima, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Nakayama
authors.affiliation: Department of Genome Function and Pathophysiology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Higashimura-cho, Fukuyama, Hiroshima, Japan.
authors.forename: Akiho
authors.initials: A
authors.lastname: Shima
authors.affiliation: Department of Genome Function and Pathophysiology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Higashimura-cho, Fukuyama, Hiroshima, Japan.
authors.forename: Arisa
authors.initials: A
authors.lastname: Uda
authors.affiliation: Department of Genome Function and Pathophysiology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Higashimura-cho, Fukuyama, Hiroshima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuoka
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Higashimura-cho, Fukuyama, Hiroshima, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kamishikiryo
authors.affiliation: Department of Genome Function and Pathophysiology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Higashimura-cho, Fukuyama, Hiroshima, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Michihara
authors.affiliation: Department of Pharmacotherapeutics, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Higashimura-cho, Fukuyama, Hiroshima, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Inoue
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000473:pathology*; D057167:Claudins / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice
chemical_list: C462524:CLDND1 protein, human; D057167:Claudins
keywords: cerebellar hemorrhage; claudin domain containing 1; endothelial cell; vascular permeability