Regulation of liver regeneration.
BACKGROUND
Hepatocyte regeneration proceeds along a sequence of distinctive phases and results in a precise reconstitution of the lost tissue mass. The molecular mechanisms regulating liver regeneration have recently been elucidated.


METHODS
Important aspects of the regulatory steps of hepatocyte proliferation during regeneration are summarized.


RESULTS
Hepatocytes normally remain in proliferative quiescence. Regeneration requires priming of hepatocytes to achieve competence for proliferation. This is the initiation phase, which is regulated by cytokines, including interleukin-6 and tumour necrosis factor-alpha. During the subsequent proliferation, the hepatocyte population is expanded (the expansion phase), it being chiefly regulated by hepatocyte growth factor and transforming growth factor-alpha. Upon sensing of the required cell mass, the proliferation response is terminated (termination phase) and is mainly mediated by transforming growth factor-beta and activins. These structured processes go in line with a remodelling response, resulting in the reconstruction of a vascularized liver lobule.


CONCLUSIONS
Liver regeneration proceeds in a highly ordered fashion, critical steps being regulated by several molecular mechanisms acting in a characteristic timely sequence.
Zimmermann
Arthur
A
Institute of Pathology of the University, Murtenstrasse 31, CH-3010 Berne, Switzerland. zimmerma@patho.unibe.ch
D000818:Animals; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000502:physiology; D022781:Hepatocytes / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D008115:Liver Regeneration / Q000502:physiology*; D051381:Rats; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D016207:Cytokines; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494088:Stat3 protein, rat; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor; D018844:Cyclin-Dependent Kinases