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 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.
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 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.
Authors: Laura Lagoudakis; Isabelle Garcin; Boris Julien; Kis Nahum; Dawidson A Gomes; Laurent Combettes; Michael H Nathanson; Thierry Tordjmann Journal: Hepatology Date: 2010-08 Impact factor: 17.425
Authors: Geneviève Dupont; Laurent Combettes; Gary S Bird; James W Putney Journal: Cold Spring Harb Perspect Biol Date: 2011-03-01 Impact factor: 10.005
Authors: Mateus T Guerra; Emerson A Fonseca; Flavia M Melo; Viviane A Andrade; Carla J Aguiar; Lídia M Andrade; Ana Cristina N Pinheiro; Marisa C F Casteluber; Rodrigo R Resende; Mauro C X Pinto; Simone O A Fernandes; Valbert N Cardoso; Elaine M Souza-Fagundes; Gustavo B Menezes; Ana M de Paula; Michael H Nathanson; Maria de Fátima Leite Journal: Hepatology Date: 2011-07 Impact factor: 17.425
Authors: Tanaporn Khamphaya; Natsasi Chukijrungroat; Vitoon Saengsirisuwan; Kisha A Mitchell-Richards; Marie E Robert; Albert Mennone; Meenakshisundaram Ananthanarayanan; Michael H Nathanson; Jittima Weerachayaphorn Journal: Hepatology Date: 2018-01-02 Impact factor: 17.425