title: Mir-203-mediated tricellulin mediates lead-induced in vitro loss of blood-cerebrospinal fluid barrier (BCB) function.
abstract: The blood-cerebrospinal fluid barrier (BCB) plays a critical role in the maintenance of optimal brain function. Tricellulin (TRIC), a protein localized at the tricellular contact sites of epithelial cells is involved in the formation of tight junctions in various epithelial barriers. However, little is known about its expression in the choroidal epithelial cells. It is well established that lead (Pb) exposure increases the leakage of the BCB. The purpose of this study is to investigate the expression and localization of TRIC in choroidal epithelial cells in vitro and whether altered TRIC expression mediates Pb-induced loss of barrier function. We found that TRIC protein and mRNA were expressed in choroidal epithelial cells in vitro and TRIC was localized at the tricellular contacts, colocalizing with occludin. Downregulation of TRIC by siRNA increased the BCB permeability corroborated by altered transendothelial electrical resistance (TEER) and FITC-dextran flux. Treatment with 10μM Pb reduced TRIC protein expression, but overexpression of TRIC alleviated the Pb-induced increase in BCB permeability. Bioinformatics analysis showed that mir-203 was a potential microRNA (miRNA) binding motif on TRIC 3'UTR, and that Pb exposure increased the expression of mir-203. Treatment with a mir-203 inhibitor increased TRIC protein expression and attenuated the Pb-induced BCB leakage. Our results establish that TRIC plays an important role in regulating BCB function.
authors.affiliation: Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Su
authors.affiliation: Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zipeng
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.affiliation: Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China. Electronic address: luowenj@fmmu.edu.cn.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Luo
mesh_terms: D000818:Animals; D001769:Blood; D002460:Cell Line; D002555:Cerebrospinal Fluid; D002831:Choroid Plexus / Q000166:cytology / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D007854:Lead / Q000633:toxicity*; D062794:MARVEL Domain Containing 2 Protein / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D051381:Rats
chemical_list: D062794:MARVEL Domain Containing 2 Protein; C575934:MIRN203 microRNA, mouse; D035683:MicroRNAs; D007854:Lead
keywords: Blood–cerebrospinal fluid barrier; Lead; Tricellulin