42.4:
Liver Regeneration
In vertebrates, the liver is the only organ that can regenerate after injury, infection, or partial surgical removal.
Approximately 80% of the liver mass is hepatocytes — cells responsible for most liver functions. These cells remain in the G0 phase of the cell cycle unless stimulated.
Upon injury, Kupffer cells — phagocytic cells lining specialized capillary channels in the liver, release IL-6 and TNF-α. These cytokines induce hepatocytes to express c-MET and EGF receptors on their cell surface.
Then, the local stellate cells and the duodenum release hepatocyte growth factors and epidermal growth factors.
HGF and EGF enter the injury site through the bloodstream to bind their receptors, c-MET and EGFR, on the primed hepatocytes.
As a result, the hepatocytes overcome the G0/G1 cell cycle checkpoint and start proliferating at the injury site to heal the damaged tissue.
Once the necessary organ size and tissue architecture are restored, stellate cells release TGF-β to block hepatocyte proliferation and terminate regeneration.
42.4:
Liver Regeneration
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large polyhedral-shaped epithelial cells that store glycogen, vitamin B12, folic acid, and iron. In contrast, the stellate cells, typically present in the space of Disse, have a star-like shape and store vitamin A. The sinusoidal endothelial cells are responsible for forming the walls of blood vessels that transport the blood through the liver. The Kupffer cells are specialized macrophages attached to the sinusoidal endothelial cells. They are involved in killing bacteria and removing aged erythrocytes.
Cytokines and Growth Factors Involved in Liver Regeneration
Liver regeneration is a highly organized process that involves three phases; the priming, proliferative, and termination phase. In response to an injury, the Kupffer and stellate cells actively release cytokines and growth factors. The cytokines include interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which prime the hepatocytes to become receptive to growth factors. The growth factors include epidermal growth factor (EGF), transforming growth factors (TGF), and hepatocyte growth factor (HGF). These growth factors trigger the hepatocytes to pass the cell cycle checkpoint and proliferate. Other factors such as insulin from the pancreas, norepinephrine from the adrenal gland, and triiodothyronine from the thyroid gland also facilitate the hepatocytes to pass the G0/G1 cell cycle checkpoint. These hepatocytes then enter the S phase, proliferate, and regenerate the liver.
Suggested Reading
- Michalopoulos, George K. "Liver regeneration." Journal of cellular physiology 213.2 (2007): 286-300.