title: Use of cell-based screening to identify small-molecule compounds that modulate claudin-4 expression.
abstract: Claudins constitute a family of at least 27 proteins with four transmembrane domains, and play a pivotal role in maintaining tight-junctions seals in diverse epithelial tissues. The expression of claudin-4 often changes in intestinal tissues of inflammatory bowel disease and various human cancers. Therefore, claudin-4 is a promising target for treatment of these diseases. In our previous study, we established a reporter cell line to monitor claudin-4 expression on the basis of a functional claudin-4 promoter. Using this cell line, we have performed a cell-based screen of a library containing 2642 biologically active small-molecule compounds to identify modulators of claudin-4 expression. The screen identified 24 potential modulators of the claudin-4 promoter activity. Fourteen of these compounds (12 of them novel) induced endogenous claudin-4 expression. The identified compounds might serve as lead compounds targeting aberrant gene expression in inflammatory bowel disease.
authors.affiliation: Laboratory of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, 565-0871, Japan, akihiro@phs.osaka-u.ac.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Watari
authors.forename: Maki
authors.initials: M
authors.lastname: Hashegawa
authors.forename: Thanchanok
authors.initials: T
authors.lastname: Muangman
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Yagi
authors.forename: Masuo
authors.initials: M
authors.lastname: Kondoh
mesh_terms: D002460:Cell Line; D062506:Claudin-4 / Q000096:biosynthesis*; D003584:Cytological Techniques / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation
chemical_list: D062506:Claudin-4