Knockdown of tight junction protein claudin-2 prevents bile canalicular formation in WIF-B9 cells |
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Authors: | Seiichi Son Takashi Kojima Catherine Decaens Hiroshi Yamaguchi Tatsuya Ito Masafumi Imamura Masaki Murata Satoshi Tanaka Hideki Chiba Koichi Hirata Norimasa Sawada |
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Institution: | (1) Departments of Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan;(2) Departments of Pathology, Sapporo Medical University School of Medicine, S1, W17, Sapporo 060-8556, Japan;(3) INSERM, U757, 91405 Orsay, France;(4) Univ Paris-Sud, UMR-S757, 91405 Paris, France |
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Abstract: | The polarization of hepatocytes involves formation of functionally distinct sinusoidal (basolateral) and bile canalicular
(apical) plasma membrane domains that are separated by tight junctions. Although various molecular mechanisms and signaling
cascades including polarity complex proteins may contribute to bile canalicular formation in hepatocytes, the role of tight
junction proteins in bile canalicular formation remains unclear. To investigate the role of the integral tight junction protein
claudin-2 in bile canalicular formation, we depleted claudin-2 expression by siRNA in the polarized hepatic cell line WIF-B9
after treatment with or without phenobarbital. When WIF-B9 cells were treated with phenobarbital, claudin-2 expression and
tight junction strands were markedly increased together with induction of canalicular formation with a biliary secretion function.
Knockdown of claudin-2 prevented bile canalicular formation after treatment with or without phenobarbital. Furthermore, knockdown
of claudin-2 caused a change from a hepatic polarized phenotype to a simple polarized phenotype, together with upregulation
of pLKB1, pMAPK, pAkt and pp38 MAPK, but not pMLC, PTEN or cdc42, and an increase of intracellular vacuoles, which were present
before bile canalicular formation. These results suggest that claudin-2 may affect not only the bile canalicular seal but
also bile canalicular formation. |
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Keywords: | Hepatic cell polarity Bile canaliculi Tight junctions siRNA Phenobarbital Signal transduction |
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