Remodelling of calcium signalling during liver regeneration in the rat

Background/Aims: During liver regeneration, a network of cytokines and growth factors interact with hepatocytes, helping to restore the liver mass and functions after partial tissue loss. Agonists that trigger Ca2+ signals in the liver contribute to this process, although little is known about calcium signalling during liver regeneration. Results: We observed two phases in which the hepatocyte response to calcium-mobilising agonists was greatly reduced versus control cells at 24 h and five days after partial hepatectomy. We found that both phases of hepatocyte desensitisation involved the down-regulation of cell surface receptors and the type II InsP(3) receptor. Single cell studies with flash photolysis of caged InsP3 revealed that InsP(3)-mediated Ca2+ release was slower in regenerating hepatocytes at 24, 48 h and 5 days than in control cells. Also, the temporal pattern of vasopressin-elicited intracellular calcium oscillations studied on fura2-loaded cells was altered, with the duration of each Ca2+ peak being longer. Finally, we showed an association between hepatocyte desensitisation and progression through the cell cycle towards the S phase at 24 h after hepatectomy. Conclusions: Our study supports the remodelling of hepatocyte calcium signalling during liver regeneration, and that this change is partly linked with cell cycle progression. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.