Role of the p38 MAP-kinase signaling pathway for Cx32 and claudin-1 in the rat liver.
Liver regeneration and cholestasis are associated with adaptive changes in expression of gap and tight junctions through signal transduction. The roles of stress responsitive MAP-kinase, p38 MAP-kinase, in the signaling pathway for gap junction protein, Cx32, and tight junction protein, claudin-1, were examined in rat liver in vivo and in vitro, including regeneration following partial hepatectomy and cholestasis after common bile duct ligation. Changes in the expression and function of Cx32 and claudin-1 in hepatocytes in vivo were studied using the p38 MAP-kinase inhibitor SB203580. Following partial hepatectomy and common bile duct ligation, down-regulation of Cx32 protein was inhibited by SB203580 treatment. Up-regulation of claudin-1 protein was enhanced by SB203580 treatment after partial hepatectomy but not common bile duct ligation. However, no change of the Ki-67 labeling index (which is a marker for cell proliferation) in the livers treated with SB203580, was observed compared to that without SB203580 treatment. In primary cultures of rat hepatocytes, however, treatment with a p38 MAP-kinase activator, anisomycin, decreased Cx32 and claudin-1 protein levels. p38 MAP-kinase may be an important signaling pathway for regulation of gap and tight junctions in hepatocytes. Changes of gap and tight junctions during liver regeneration and cholestasis are shown to be in part controlled via the p38 MAP-kinase signaling pathway and are independent of cell growth.
Kojima
Takashi
T
Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. ktakashi@sapmed.ac.jp
Yamamoto
Toshinobu
T
Murata
Masaki
M
Lan
Mengdong
M
Takano
Ken-Ichi
K
Go
Mitsuru
M
Ichimiya
Shingo
S
Chiba
Hideki
H
Sawada
Norimasa
N
D000818:Animals; D002478:Cells, Cultured; D002779:Cholestasis / Q000601:surgery; D062445:Claudin-1; D017630:Connexins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008115:Liver Regeneration / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D019108:Tight Junctions / Q000378:metabolism; D000097002:Gap Junction beta-1 Protein
D062445:Claudin-1; D017630:Connexins; D004791:Enzyme Inhibitors; D007093:Imidazoles; D008565:Membrane Proteins; D011725:Pyridines; D000097002:Gap Junction beta-1 Protein; C568114:Cldn1 protein, rat; C093642:SB 203580