Remodelling of calcium signalling during liver regeneration in the rat.
OBJECTIVE
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 24h 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 InsP3 receptor. Single cell studies with flash photolysis of caged InsP3 revealed that InsP3-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.
Nicou
Alexandra
A
INSERM U.757, Université Paris Sud, bât. 443, 91405 Orsay, France. anicou@unav.es
Serrière
Valérie
V
Hilly
Mauricette
M
Prigent
Sylvie
S
Combettes
Laurent
L
Guillon
Gilles
G
Tordjmann
Thierry
T
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002453:Cell Cycle; D015536:Down-Regulation; D005260:Female; D006498:Hepatectomy; D022781:Hepatocytes / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000032:analysis / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000819:agonists / Q000032:analysis / Q000378:metabolism
D053496:Inositol 1,4,5-Trisphosphate Receptors; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D002118:Calcium