Liver regeneration

Liver regeneration is the process by which the liver is able to replace lost liver tissue from growth from the remaining tissue. The liver is the only visceral organ that possesses the capacity to regenerate.[1][2] The liver can regenerate after either surgical removal or after chemical injury.[3] It is known that as little as 25% of the original liver mass can regenerate back to its full size.[2][4] The process of regeneration in mammals is mainly compensatory growth because only the mass of the liver is replaced, not the shape.[5] However, in lower species such as fish, both liver size and shape can be replaced.[6]

Mechanism

Liver regeneration involves replication of the liver cells, mainly hepatocytes, followed by other cells such as biliary epithelial cells and sinusoidal endothelial cells. Once cell proliferation is completed, the newly divided cells undergo restructuring, angiogenesis and reformation of extracellular matrix to complete the regeneration process.[2] In most cases, liver function is only partially affected during liver regeneration. Whereas certain specialized functions such as drug metabolism decrease, many other primary functions such as albumin and bile production are not substantially affected.[1]

Liver regeneration is a highly controlled process regulated by a complex network on highly redundant signals. Several signaling pathways are known to stimulate regeneration in the liver including cytokines, growth factors, hormones, and nuclear receptors.[1] Discovered and studying in vivo some natural multicomponent liver regeneration substances – hepatic stimulator substance,[7] hepatic regeneration set,[8] augmenter of liver regeneration.[9]

Function

The ability for the liver to regenerate is central to liver homeostasis. Because the liver is the main site of drug detoxification, it is exposed to many chemicals in the body which may potentially induce cell death and injury. The liver can regenerate damaged tissue rapidly thereby preventing its own failure. However, a predictor of the true speed of liver regeneration depends on whether Interleukin 6 has overexpression[10]. Liver regeneration is also critical for patients of liver diseases where the partial removal of the liver due to fibrosis or tumor is a common therapy that utilizes the ability of the remaining liver to generate back.

Experimental models

Two main types of models are used to study liver regeneration, including surgical removal, also referred to as partial hepatectomy (PHX), and chemical-induced liver damage. Whereas the mechanisms and kinetics of liver regeneration in these two models are different, many of the same signaling pathways stimulate liver regeneration in both pathways.[11]

References

  1. 1 2 3 Michalopoulos GK (2013). "Principles of Liver Regeneration and Growth Homeostasis". Comprehensive Physiology. 3. pp. 485–513. doi:10.1002/cphy.c120014. ISBN 978-0-470-65071-4. PMID 23720294.
  2. 1 2 3 Michalopoulos GK, DeFrances MC (April 1997). "Liver regeneration". Science. 276 (5309): 60–6. doi:10.1126/science.276.5309.60. PMC 2701258. PMID 9082986.
  3. ↑ Mehendale HM (2005). "Tissue repair: an important determinant of final outcome of toxicant-induced injury". Toxicologic Pathology. 33 (1): 41–51. doi:10.1080/01926230590881808. PMID 15805055.
  4. ↑ Fausto N, Campbell JS, Riehle KJ (February 2006). "Liver regeneration". Hepatology. 43 (2 Suppl 1): S45–53. doi:10.1002/hep.20969. PMID 16447274.
  5. ↑ Fausto N (2000). "Liver regeneration". Journal of Hepatology. 32 (1 Suppl): 19–31. doi:10.1016/S0168-8278(00)80412-2. PMID 10728791.
  6. ↑ Chu J, Sadler KC (November 2009). "New school in liver development: lessons from zebrafish". Hepatology. 50 (5): 1656–63. doi:10.1002/hep.23157. PMC 3093159. PMID 19693947.
  7. ↑ LaBrecque DR (May 1991). "Hepatic stimulator substance. Discovery, characteristics and mechanism of action". Digestive Diseases and Sciences. 36 (5): 669–73. doi:10.1007/bf01297036. PMID 2022169.
  8. ↑ Gal Perin EI, Ataullakhanov RI, Dyuzheva TG, Platonova LV, Melnikova TM, Monakov MY, Dudchenko AM, Lyundup AV, Klabukov ID (October 2017). "[Possible use of the growing liver biological set for hepatic recovery after toxic damage (an experimental study)]". Biomeditsinskaia Khimiia. 63 (5): 440–446. PMID 29080878.
  9. ↑ Nalesnik MA, Gandhi CR, Starzl TE (July 2017). "Augmenter of liver regeneration: A fundamental life protein". Hepatology. 66 (1): 266–270. doi:10.1002/hep.29047. PMC 5682950. PMID 28085209.
  10. ↑ Tachibana S, Zhang X, Ito K, Ota Y, Cameron AM, Williams GM, Sun Z (February 2014). "Interleukin-6 is required for cell cycle arrest and activation of DNA repair enzymes after partial hepatectomy in mice". Cell & Bioscience. 4 (1): 6. doi:10.1186/2045-3701-4-6. PMC 3922598. PMID 24484634.
  11. ↑ Mehendale HM, Apte U (2010). "Liver Regeneration and Tissue Repair". Comprehensive Toxicology. pp. 339–67. doi:10.1016/B978-0-08-046884-6.01013-7. ISBN 978-0-08-046884-6.

Further reading

  • Taub R (October 2004). "Liver regeneration: from myth to mechanism". Nature Reviews. Molecular Cell Biology. 5 (10): 836–47. doi:10.1038/nrm1489. PMID 15459664.
  • Michalopoulos GK (February 1990). "Liver regeneration: molecular mechanisms of growth control". FASEB Journal. 4 (2): 176–87. PMID 2404819. Republished as: Michalopoulos GK (1992). "Liver Regeneration: Molecular Mechanisms of Growth Control". Artificial Liver Support. pp. 72–93. doi:10.1007/978-3-642-77359-4_6. ISBN 978-3-642-77361-7.
  • Matsumoto K, Nakamura T (1992). "Hepatocyte growth factor: molecular structure, roles in liver regeneration, and other biological functions". Critical Reviews in Oncogenesis. 3 (1–2): 27–54. PMID 1312869.
  • Fausto N, Laird AD, Webber EM (December 1995). "Liver regeneration. 2. Role of growth factors and cytokines in hepatic regeneration". FASEB Journal. 9 (15): 1527–36. PMID 8529831.
  • Jirtle, Randy L., ed. (1995). Liver Regeneration and Carcinogenesis: Molecular and Cellular Mechanisms. Academic Press. ISBN 978-0-08-053554-8.
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