title: Oncostatin M induces upregulation of claudin-2 in rodent hepatocytes coinciding with changes in morphology and function of tight junctions.
abstract: In rodent livers, integral tight junction (TJ) proteins claudin-1, -2, -3, -5 and -14 are detected and play crucial roles in the barrier to keep bile in bile canaculi away from the blood circulation. Claudin-2 shows a lobular gradient increasing from periportal to pericentral hepatocytes, whereas claudin-1 and -3 are expressed in the whole liver lobule. Although claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells, the physiological functions and regulation of claudin-2 in hepatocytes remain unclear. Oncostatin M (OSM) is a multifunctional cytokine implicated in the differentiation of hepatocytes that induces formation of E-cadherin-based adherens junctions in fetal hepatocytes. In this study, we examined whether OSM could induce expression and function of claudin-2 in rodent hepatocytes, immortalized mouse and primary cultured proliferative rat hepatocytes. In the immortalized mouse and primary cultured proliferative rat hepatocytes, treatment with OSM markedly increased mRNA and protein of claudin-2 together with formation of developed networks of TJ strands. The increase of claudin-2 enhanced the paracellular barrier function which depended on molecular size. The increase of claudin-2 expression induced by OSM in rodent hepatocytes was regulated through distinct signaling pathways including PKC. These results suggest that expression of claudin-2 in rodent hepatocytes may play a specific role as controlling the size of paracellular permeability in the barrier to keep bile in bile canaculi.
authors: Department of Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Masafumi
authors: M
authors: Imamura
authors: Takashi
authors: T
authors: Kojima
authors: Mengdong
authors: M
authors: Lan
authors: Seiichi
authors: S
authors: Son
authors: Masaki
authors: M
authors: Murata
authors: Makoto
authors: M
authors: Osanai
authors: Hideki
authors: H
authors: Chiba
authors: Koichi
authors: K
authors: Hirata
authors: Norimasa
authors: N
authors: Sawada
mesh_terms: D000818:Animals; D001648:Bile Canaliculi / Q000502:physiology / Q000648:ultrastructure; D002450:Cell Communication / Q000502:physiology; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002463:Cell Membrane Permeability / Q000502:physiology*; D002478:Cells, Cultured; D057167:Claudins; D005786:Gene Expression Regulation / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008833:Microcirculation / Q000502:physiology / Q000648:ultrastructure; D008970:Molecular Weight; D053683:Oncostatin M / Q000494:pharmacology / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D057167:Claudins; C113371:Cldn2 protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D053683:Oncostatin M; D011493:Protein Kinase C