title: Changes in protein and mRNA expression levels of claudin family after mucosal lesion by intestinal ischemia/reperfusion.
abstract: Ischemia/reperfusion (I/R) injury of the intestine is the leading cause of organ dysfunction after restoration of blood flow after diverse events, including shock and intestinal transplantation. I/R injury must be overcome for successful small intestinal transplantation. Tight junctions (TJ) are the most apical component of the intercellular junctional complex in epithelial cells; they establish cell polarity and functioning as major determinants of epithelial barrier function. Among the proteins that comprise TJ, the claudin family is thought to play a crucial role in homeostasis in multicellular organisms. Therefore, the aim of this study was to examine the changes in function of TJ and behavior of the claudin family during intestinal I/R. Wistar/ST rats underwent intestinal ischemia by using the spring scale and surgical suture for 1h, followed by 24h of reperfusion. We examined the changes in area under the blood concentration curve (AUC) after oral administration of FD-4, which is a paracellular marker, and claudin-1, -2, -4, and -7 mRNA and protein expression levels in ileum. The structure of ileal mucosa was partly damaged and its function was diminished by intestinal I/R until 3h after reperfusion, but were almost recovered 24h after reperfusion. However, a time difference was shown between the recoveries of mucosal structure and function. Furthermore, a difference in the expression among various kinds of claudin was found. It was suggested that claudin-4 and multi-PDZ domain protein, which is a scaffolding protein, regulate intestinal paracellular permeability during intestinal I/R. Moreover, the changes in the expression level of claudin-2 were unique.
authors.affiliation: Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. Electronic address: takizawa@toyaku.ac.jp.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takizawa
authors.affiliation: Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Hisanao
authors.initials: H
authors.lastname: Kishimoto
authors.affiliation: Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kitazato
authors.affiliation: Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Tomita
authors.affiliation: Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hayashi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D003911:Dextrans / Q000008:administration & dosage / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000493:pharmacokinetics; D005786:Gene Expression Regulation; D007082:Ileum / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010539:Permeability; D010743:Phospholipids / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019108:Tight Junctions / Q000378:metabolism* / Q000473:pathology
chemical_list: D057167:Claudins; D003911:Dextrans; D005456:Fluorescent Dyes; D010743:Phospholipids; D012333:RNA, Messenger; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate