Inhibition of extracellular signal-regulated kinase downregulates claudin-2 expression and alters paracellular permeability in mouse rectum CMT93-II cells

• Published in: Tissue & cell 2013-06, Vol.45 (3), p.175-182
• Main Authors: Inai, Tetsuichiro, Kitagawa, Norio, Hatakeyama, Yuji, Ikebe, Tetsuro, Iida, Hiroshi, Fujita, Mamoru
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; Butadienes - pharmacology; Cell Line; Cell Membrane Permeability - drug effects; Claudin-2; Claudin-2 - biosynthesis; Down-Regulation - drug effects; Electric Impedance; Epithelial Cells - cytology; Epithelial Cells - metabolism; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Extracellular Signal-Regulated MAP Kinases - metabolism; Gene Expression Regulation - drug effects; Mice; Mitogen-activated protein kinase; Nitriles - pharmacology; Rectum - cytology; Rectum - metabolism; Signal Transduction; Transepithelial electrical resistance; U0126
• ISSN: 0040-8166; 1532-3072
• DOI: 10.1016/j.tice.2012.11.001

Abstract The morphological and physiological properties of tight junctions (TJs) are determined by the combination and mixing ratios of claudin species. Mouse rectum carcinoma cell lines, CMT93-I and -II cells, expressed claudin-4, -6, -7, and -12, and CMT93-II cells further expressed claudin-2. Although there were no differences in the morphology and number of TJ strands between the two cell lines, transepithelial electrical resistance (TER) of CMT93-II cells was approximately one-seventh that of CMT93-I cells. In this study, we aimed to determine whether claudin-2 expression in CMT93-II cells caused the reduction of TER. Inhibition of the extracellular signal-regulated kinase (ERK) pathway by U0126 treatment for 24 and 48 h in CMT93-II cells markedly decreased claudin-2 from the apical junctional region and increased TER. However, claudin-4, -6, and -7 were still continuously localized at the apical junctional region by U0126 treatment. Moreover, the claudin-2 expression recovered at the apical junctional region after the removal of U0126 and TER decreased almost to the baseline level. These results suggest that the ERK pathway positively regulates claudin-2 protein expression and claudin-2 is involved in lowering TER in CMT93-II cells.