Inhibition of extracellular signal-regulated kinase downregulates claudin-2 expression and alters paracellular permeability in mouse rectum CMT93-II cells.
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 48h 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.
Department of Morphological Biology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan. tinaitj@college.fdcnet.ac.jp
Tetsuichiro
T
Inai
Norio
N
Kitagawa
Yuji
Y
Hatakeyama
Tetsuro
T
Ikebe
Hiroshi
H
Iida
Mamoru
M
Fujita
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects*; D062446:Claudin-2 / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects; D017097:Electric Impedance; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D009570:Nitriles / Q000494:pharmacology; D012007:Rectum / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction
D002070:Butadienes; D062446:Claudin-2; D009570:Nitriles; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases