Regeneration of liver cells

Ability to perform liver regeneration is a process which is very important so that the liver can recover from damage inflicted from detoxification and immunological processes. Regeneration is achieved with a very complex interaction between the cells contained in the liver, hepatocytes, Kupffer cells, sinusoidal endothelial cells, Ito cells and stem cells; with extra-hepatic organs, thyroid gland, adrenal gland, pancreas, duodenum, hypothalamus.
Hepatocytes, the cells are very unique. Proliferative potential of hepatocytes to perform, appearing at times of loss of cell mass, called the prime phase or phase replicative competence and is generally triggered by Kupffer cells through sitokina secretion of IL-6 and TNF-α. In this phase, hepatocytes enter the cell cycle from G0 phase to G1 phase.
TNF-α may provide or apoptotik proliferative effects, depending on the reactive oxygen species and glutathione, at least four transcription factors are activated before hepatocytes enter into the proliferative phase, namely NFkappaB, STAT3, AP-1 and C / EBPbeta.
Hepatocyte proliferation induced by stimulation sitokina HGF and TGF-α, and EGF with two paths. HGF, TGF-α, and EGF are growth factors derived from Serine and protein substrate metal that induces DNA synthesis of the first path is the path IL-6/STAT3 a role in cell cycle through cyclin D1/p21 and protection of cells by increasing the ratio of FLIP, Bcl-2, Bcl-XL, Ref1, and MnSOD. The second path is the path PI3-K/PDK1/Akt that controls cell size through mTOR molecules, other than as an anti-apoptotic substances and antioxidants.
Tri-iodotironina hormones, in addition to lowering cholesterol in the liver, also have the capacity in the proliferation of hepatocytes as a mitogen which acts on cyclin D1, accelerate the O2 consumption by mitochondria and increased production of reactive oxygen species. ROS secretion into the hepatocyte cytoplasm activates transcription factor NF-kappaB. In Kupffer cells, ROS in the cytoplasm, activates the secretion of TNF-α sitokina, IL-6 and IL-1 for secretion. Bonding that occurred between the three sitokina this will induce the expression of hepatocyte pencerap antioxidant enzymes, such as manganese superoxide dismutase, nitric oxide synthase-i, anti-apoptotic protein Bcl-2, haptoglobin and fibrinogen-β in the proliferation of hepatocytes required. [14] Stress can cause oxidative damage by ROS and that can be caused by various sitokina, can be eliminated with tosoferol intake (100 mg / kg) or compound inhibitors gadolinium chloride (10 mg / kg) as owned by Kupffer cells, before stimulation hormone tri-iodotironina , while the rate of hepatocyte proliferation is controlled by the concentration hepatotrofik etanolamina as humoral factors.
Ability of the liver to regenerate has been known since ancient Greece from the mythical story about a titan named Prometheus. This capability can be vanished, until hepatocytes are not able to enter into the cell cycle, despite losing some of its mass, in case of liver fibrosis. Jogging fibrosis who do not get immediate care, will gradually develop into cirrhosis of the liver and requires the sufferer to undergo liver transplantation or hepatektomi for survival.
Liver regeneration after partial hepatektomi is a very complicated process under the influence of changes hemodinamika, modulation sitokina, hormones and growth factor activation of transcription factors, which lead to the process of mitosis. PRL hormone secreted by the pituitary gland hepatotrofik as mitogen induced responses that play a role in the process of proliferation and differentiation. PRL giving effect to the increased activity of transcription factors that play a role in cell proliferation, such as AP-1, c-Jun and STAT-3, and differentiation and the maintenance of metabolism, such as CEBP-alpha, HNF-1, HNF-4 and HNF-3. c-Jun is one of the authors of AP-1 proteins. Induction of NFkappaB in this phase is required to prevent apoptosis and cell cycle triggers a reasonable pace.