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Keywords:

  • hepatic oval cell;
  • homing;
  • phosphatidylinositol-3-kinase;
  • somatostatin;
  • somatostatin receptor type 4

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.

Aims

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.

Conclusion

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.