title: Somatostatin stimulates the migration of hepatic oval cells in the injured rat liver.
abstract: BACKGROUND
  Somatostatin is a pleiotropic peptide, exerting a variety of effects through its receptor subtypes. Recently, somatostatin has been shown to act as a chemoattractant for haematopoietic progenitor cells and hepatic oval cells (HOC) via receptor subtype 2 and subtype 4 (SSTR4) respectively.
  
  
  OBJECTIVE
  We investigated the in vivo effect of somatostatin/SSTR4 on HOC migration in the injured liver model of rats and the type of signalling molecules associated with the chemotactic function.
  
  
  METHODS
  Migration assay, HOC transplantation and phosphatidylinositol-3-kinase (PI3K) signalling were assessed with or without somatostatin and an analogue of somatostatin (TT232) that specifically binds to SSTR4.
  
  
  RESULTS
  TT232 was shown to have an antimigratory action on HOC induced by somatostatin in vitro. In HOC transplantation experiments, a lower number of donor-derived cells were detected in TT232-treated animals, as compared with control animals. Activation of PI3K was observed in HOC exposed to somatostatin, and this activation was suppressed by either SSTR4 antibody or TT232-pretreatment. In addition, a PI3K inhibitor abrogated the motility of HOC.
  
  
  CONCLUSIONS
  Together, these data suggest that somatostatin stimulates the migration of HOC within injured liver through SSTR4, and this action appears to be mediated by the PI3K pathway.
authors.affiliation: Department of Biological Sciences, Pusan National University, Pusan, Korea. y.jung@pusan.ac.kr
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Jung
authors.forename: Seh-Hoon
authors.initials: SH
authors.lastname: Oh
authors.forename: Rafal P
authors.initials: RP
authors.lastname: Witek
authors.forename: Bryon E
authors.initials: BE
authors.lastname: Petersen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D017690:Cell Transplantation; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017481:Receptors, Somatostatin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000378:metabolism / Q000494:pharmacology* / Q000031:analogs & derivatives
chemical_list: D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; C098681:somatostatin receptor subtype-4; C094462:TT2-32; D013004:Somatostatin; D058539:Phosphatidylinositol 3-Kinase
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