Molecular mechanisms of liver regeneration and protection for treatment of liver dysfunction and diseases
- PMID: 20607568
- DOI: 10.1007/s00534-010-0304-2
Molecular mechanisms of liver regeneration and protection for treatment of liver dysfunction and diseases
Abstract
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.
Similar articles
-
The survival pathways phosphatidylinositol-3 kinase (PI3-K)/phosphoinositide-dependent protein kinase 1 (PDK1)/Akt modulate liver regeneration through hepatocyte size rather than proliferation.Hepatology. 2009 Jan;49(1):204-14. doi: 10.1002/hep.22583. Hepatology. 2009. PMID: 19065678
-
Cellular and molecular mechanisms of liver regeneration: Proliferation, growth, death and protection of hepatocytes.Semin Cell Dev Biol. 2020 Apr;100:62-73. doi: 10.1016/j.semcdb.2019.10.007. Epub 2019 Oct 25. Semin Cell Dev Biol. 2020. PMID: 31669133 Review.
-
Compensatory recovery of liver mass by Akt-mediated hepatocellular hypertrophy in liver-specific STAT3-deficient mice.J Hepatol. 2005 Nov;43(5):799-807. doi: 10.1016/j.jhep.2005.03.027. Epub 2005 May 31. J Hepatol. 2005. PMID: 16083985
-
Rapid activation of protein kinase B/Akt has a key role in antiapoptotic signaling during liver regeneration.Biochem Biophys Res Commun. 2000 Dec 29;279(3):974-9. doi: 10.1006/bbrc.2000.4044. Biochem Biophys Res Commun. 2000. PMID: 11162460
-
[Role of jak/STAT3 and PI3-K/Akt pathways in liver injury and regeneration].Seikagaku. 2008 May;80(5):399-408. Seikagaku. 2008. PMID: 18575225 Review. Japanese. No abstract available.
Cited by
-
Liver regeneration after injury: Mechanisms, cellular interactions and therapeutic innovations.Clin Transl Med. 2024 Aug;14(8):e1812. doi: 10.1002/ctm2.1812. Clin Transl Med. 2024. PMID: 39152680 Free PMC article. Review.
-
Hypoxic Conditioned Medium From Human Adipose-Derived Stem Cells Promotes Mouse Liver Regeneration Through JAK/STAT3 Signaling.Stem Cells Transl Med. 2016 Jun;5(6):816-25. doi: 10.5966/sctm.2015-0191. Epub 2016 Apr 21. Stem Cells Transl Med. 2016. PMID: 27102647 Free PMC article.
-
Effects of hepatic blood inflow on liver ultrastructure and regeneration after extensive liver resection in rats with cirrhosis.Exp Ther Med. 2018 Sep;16(3):2573-2583. doi: 10.3892/etm.2018.6467. Epub 2018 Jul 18. Exp Ther Med. 2018. PMID: 30210605 Free PMC article.
-
Toll-like receptor 5-mediated signaling enhances liver regeneration in mice.Mil Med Res. 2021 Feb 23;8(1):16. doi: 10.1186/s40779-021-00309-4. Mil Med Res. 2021. PMID: 33622404 Free PMC article.
-
Understanding immunological insights of liver transplantation: a practice for attaining operational tolerance.Clin Exp Immunol. 2025 Jan 21;219(1):uxae125. doi: 10.1093/cei/uxae125. Clin Exp Immunol. 2025. PMID: 39973343 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous