Liver intoxications switch on proliferation of the hepatocytes

  • We are exposed to many toxins every day. These toxins enter the blood and subsequently from blood they are removed by the liver (and the liver binds the toxins from the blood). Alcohol, paracetamol, aspirin, (and other medications), smoking, internal toxins (from inflammation in other organs), in some cases viruses and bacteria are all toxins that must be detoxified by the liver.

  • During this process of detoxification, some liver cells do not survive and die. Everyday, many liver cells die and we lose hepatocytes. However, our liver has a tremendous capacity to produce healthy hepatocytes instead of dead ones in a process called regeneration.

  • When the liver is challenged by intoxication and tissue loss, a regenerative process is initiated. Hepatocytes usually shift from a resting phase (G0 phase), in which cells exist in a quiescent state, to an activated state (G1 phase), and start to divide (proliferate). The hepatocyte division (cell cycle) is controlled by several factors.

  • A variety of signals (proteins) from outside of the cell including hepatocyte growth factor (HGF), epidermal growth factor (EGF), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), and transforming growth factor β (TGF-β) orchestrate the progression through the cell cycle.
  • These signals are integrated during the G1 phase of the cell cycle, where cells commit to division and transition into the S phase (synthesis phase). During this phase, the complete DNA in the hepatocyte is synthesized and therewith duplicated.

  • After the S phase, hepatocytes transit into the G2 phase and synthesise important proteins for next phase.

  • During the next phase, the M phase (mitosis phase), hepatocytes produce two cells out of one and therewith hepatocytes divide (proliferate).

  • During these events, hepatocytes proliferate, shift to the regions of dead hepatocytes and therewith replace dead hepatocytes. The whole process of regeneration starting from sensing toxic components from dead cells, starting proliferation and shifting in the regions of dead is well orchestrated by hundreds of players (molecular and cellular).
  • Authors: Martin Golebiewski and Iryna Ilkavets

  • Illustration: Iryna Ilkavets

  • Animation: Ivan Savora

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