Telomerase activation and MAPK pathways in regenerating hepatocytes.
Although there have been many reports on the relationship between the activation of telomerase and carcinogenesis, the role of telomerase in normal cellular growth is still unclear. Recently, the telomerase upregulation during the process of liver regeneration has been reported, but the precise time course of its activity and factors contributing to the activation of telomerase have not yet been fully elucidated. In the present review, we demonstrate the relationship between the activation of the telomerase, the cell cycle progression and the growth-related signaling during the liver regeneration process using an in vivo mouse partial hepatectomy model. Moreover, the importance of the role of the MAPK pathways on the telomerase activity in regenerating hepatocytes is also displayed by using an in vitro culture model. In conclusion, the telomerase activity is upregulated before hepatocytes enter the S phase, and some growth factors such as EGF and HGF contribute to this process. The activation of the growth-related signaling pathways seems to play essential roles in the upregulation of the telomerase activity.
Inui
T
T
Department of Microbiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. shinomi@ndmc.ac.jp
Shinomiya
N
N
Fukasawa
M
M
Kuranaga
N
N
Ohkura
S
S
Seki
S
S
D000818:Animals; D002453:Cell Cycle; D002478:Cells, Cultured; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology* / Q000502:physiology; D008115:Liver Regeneration / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D019098:Telomerase / Q000378:metabolism*; D015854:Up-Regulation
D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D019098:Telomerase