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Molecular mechanisms of liver regeneration and protection for treatment of liver dysfunction and diseases
Author(s) -
Fujiyoshi Masato,
Ozaki Michitaka
Publication year - 2011
Publication title -
journal of hepato‐biliary‐pancreatic sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.63
H-Index - 60
eISSN - 1868-6982
pISSN - 1868-6974
DOI - 10.1007/s00534-010-0304-2
Subject(s) - liver regeneration , regeneration (biology) , protein kinase b , microbiology and biotechnology , pi3k/akt/mtor pathway , cell growth , biology , hepatocyte , hepatic stellate cell , cyclin d1 , cancer research , stem cell , hepatocyte growth factor , kupffer cell , endocrinology , signal transduction , apoptosis , cell cycle , immunology , receptor , biochemistry , in vitro , genetics
Liver regeneration is a necessary process that most liver damage depends on for recovery. Regeneration is achieved by a complex interactive network consisting of liver cells (hepatocytes, Kupffer cells, sinusoidal endothelial cells, hepatic stellate cells, and stem cells) and extrahepatic organs (thyroid gland, adrenal gland, pancreas, duodenum, and autonomous nervous system). The restoration of liver volume depends on hepatocyte proliferation, which includes initiation, proliferation, and termination phases. Hepatocytes are “primed” mainly by Kupffer cells via cytokines (IL‐6 and TNF‐alpha) and then “proliferation” and “cell growth” of hepatocytes are induced by the stimulations of cytokines and growth factors (HGF and TGF‐alpha). Liver regeneration is achieved by cell proliferation and cell growth, where the IL‐6/STAT3 and PI3‐K/PDK1/Akt pathways play pivotal roles, respectively. IL‐6/STAT3 pathway regulates hepatocyte proliferation via cyclin D1/p21 and protects against cell death by upregulating FLIP, Bcl‐2, Bcl‐xL, Ref1, and MnSOD. PI3‐K/PDK1/Akt is known to be responsible for regulation of cell size via its downstream molecules such as mTOR in addition to being known for its survival, anti‐apoptotic and anti‐oxidative properties. Although the molecular mechanisms of liver regeneration have been actively studied, the mechanisms of liver regeneration must be elucidated and leveraged for the sufficient treatment of liver diseases.