This is an, un-copyedited, author manuscript that has been accepted for publication in the Frontiers in Bioscience
The mechanisms that permit adult tissues to
regenerate are the object of intense study. Liver regeneration is a research area of considerable interest both from pathological and from physiological perspectives. One of the best models of the regenerative process is the two-thirds partial hepatectomy (PH). After PH, the remnant liver starts a series of timed responses that first favor cell growth and then halts hepatocyte proliferation once liver function is fully restored. The mechanisms regulating this process are complex and involve many cellular events.
Initiation of liver regeneration requires the injury-related cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6), and involves the activation of
cytokine-regulated transcription factors such as NF-kappaB and STAT3. An important event that takes place in the hours immediately after PH is the induction of nitric oxide synthase 2 (NOS-2) and cyclooxygenase 2 (COX-2), and the consequent release of nitric oxide (NO) and
prostaglandins (PGs). NO is involved in the vascular readaptation after PH, favoring a general permeability to growth factors throughout the organ. This review examines
the mechanisms that regulate NO release during liver regeneration and the animal models used to identify these pathways.
S.H. is a FIS program investigator supported by Instituto de Salud Carlos III (FIS 2002/3022). M.Z. is a Community of Madrid fellow. Work has been funded by
RECAVA, the Ministerio de Educación y Ciencia (SAF2002-0083 and 2005-03022), and by Fundació La Caixa (ONO3- 180-2).
Peer reviewed