fax: 206-543-3644
Liver Biology and Pathobiology
You have full text access to this OnlineOpen article
Liver regeneration†
Article first published online: 30 JAN 2006
DOI: 10.1002/hep.20969
Copyright © 2006 American Association for the Study of Liver Diseases
Issue
1527-3350/asset/cover.gif?v=1&s=3cd983af6575c8dbfd6b47a63ffa95415ace15f8)
Hepatology
Special Issue: 25th Anniversary Issue
Volume 43, Issue S1, pages S45–S53, February 2006
Additional Information
How to Cite
Fausto, N., Campbell, J. S. and Riehle, K. J. (2006), Liver regeneration. Hepatology, 43: S45–S53. doi: 10.1002/hep.20969
- †
Potential conflict of interest: Nothing to report.
Publication History
- Issue published online: 30 JAN 2006
- Article first published online: 30 JAN 2006
Funded by
- NIH. Grant Numbers: CA-23226, CA-074131
- American College of Surgeons Resident Research Scholarship
References
- 1. Liver regeneration. J Hepatol 2000; 32: 19–31.
- 2, . Liver regeneration. Science 1997; 276: 60–66.
- 3. Liver regeneration: from myth to mechanism. Nat Rev Mol Cell Biol 2004; 5: 836–847.
- 4, . Experimental pathology of the liver. Arch Pathol 1931; 12: 186–202.
- 5, . Partial hepatectomy in the mouse: technique and perioperative management. J Invest Surg 2003; 16: 99–102.
- 6. Regeneration: if they can do it, why can't we? Cell 2003; 113: 559–562.
- 7, . The role of hepatocytes and oval cells in liver regeneration and repopulation. Mech Dev 2003; 120: 117–130.
- 8. Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells. Hepatology 2004; 39: 1477–1487.Direct Link:
- 9
- 10, , . Oval cell proliferation and the origin of small hepatocytes in liver injury induced by D -galactosamine. Am J Pathol 1991; 139: 535–552.
- 11, , , . Early histological and functional alterations of ethionine liver carcinogenesis in rats fed a choline-deficient diet. Cancer Res 1978; 38: 1092–1098.
- 12, , , . A precursor-product relationship exists between oval cells and hepatocytes in rat liver. Carcinogenesis 1987; 8: 1737–1740.
- 13, . Activation, proliferation, and differentiation of progenitor cells into hepatocytes in the D-galactosamine model of liver regeneration. Am J Pathol 1993; 143: 1606–1620.
- 14, , , , , , et al. Contribution of bone marrow cells to liver regeneration after partial hepatectomy in mice. J Hepatol 2002; 36: 653–659.
- 15, , , , , , et al. Importance of cell kinetics rhythmicity for the control of cell proliferation and carcinogenesis in rat liver (review). In Vivo 1995; 9: 539–548.
- 16, , , , , . Control mechanism of the circadian clock for timing of cell division in vivo. Science 2003; 302: 255–259.
- 17. Circadian rhythms. Liver regeneration clocks on. Science 2003; 302: 234–235.
- 18, , , . The Forkhead Box m1b transcription factor is essential for hepatocyte DNA replication and mitosis during mouse liver regeneration. Proc Natl Acad Sci U S A 2002; 99: 16881–16886.
- 19, . Timing of hepatocyte entry into DNA synthesis after partial hepatectomy is cell autonomous. Proc Natl Acad Sci U S A 2000; 97: 12595–12600.
- 20, , , , , , et al. Antibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy. Am J Physiol 1992; 263: G579–585.
- 21, , , , . Acute-phase response factor, increased binding, and target gene transcription during liver regeneration. Gastroenterology 1996; 110: 1854–1862.
- 22, , , , . Increased secretion of tumour necrosis factor and interleukin 6 from isolated, perfused liver of rats after partial hepatectomy. Cytokine 2001; 13: 60–64.
- 23, , , . Rapid DNA binding by nuclear factor kappa B in hepatocytes at the start of liver regeneration. Cell Growth Differ 1995; 6: 417–427.
- 24, , . Rapid activation of the Stat3 transcription complex in liver regeneration. Hepatology 1995; 21: 1443–1449.Direct Link:
- 25, , , , , , et al. Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice. Science 1996; 274: 1379–1383.
- 26, , , . Initiation of liver growth by tumor necrosis factor: deficient liver regeneration in mice lacking type I tumor necrosis factor receptor. Proc Natl Acad Sci U S A 1997; 94: 1441–1446.
- 27, , , , , , et al. Expression of suppressors of cytokine signaling during liver regeneration. J Clin Invest 2001; 107: 1285–1292.
- 28, , , . Tumor necrosis factor primes hepatocytes for DNA replication in the rat. Hepatology 1998; 28: 1226–1234.Direct Link:
- 29, , , , , , et al. Normal liver regeneration and liver cell apoptosis after partial hepatectomy in tumor necrosis factor-alpha-deficient mice. Liver Int 2005; 25: 162–170.Direct Link:
- 30, , , , , , et al. Effect of TNF gene depletion on liver regeneration after partial hepatectomy in mice. Surgery 2001; 129: 48–54.
- 31, . TNF/LTalpha double knockout mice display abnormal inflammatory and regenerative responses to acute and chronic liver injury. Cell Tissue Res 2005; 319: 61–70.
- 32, , , , . Gene expression during the priming phase of liver regeneration after partial hepatectomy in mice. Proc Natl Acad Sci U S A 2002; 99: 11181–11186.
- 33, , , . Identification of Transcriptional Networks during Liver Regeneration. J Biol Chem 2005; 280: 3715–3722.
- 34, , , , , . Global changes in interleukin-6-dependent gene expression patterns in mouse livers after partial hepatectomy. Hepatology 2001; 33: 1377–1386.Direct Link:
- 35, , , , , . Interleukin 6 is important for survival after partial hepatectomy in mice. Hepatology 2003; 38: 674–682.Direct Link:
- 36, , , , , , et al. The IL-6-gp130-STAT3 pathway in hepatocytes triggers liver protection in T cell-mediated liver injury. J Clin Invest 2005; 115: 860–869.
- 37, , , , , , et al. Retarded liver growth in interleukin-6-deficient and tumor necrosis factor receptor-1-deficient mice. Endocrinology 2001; 142: 2953–2960.
- 38, , , , , , et al. Mitosis and apoptosis in the liver of interleukin-6-deficient mice after partial hepatectomy. Hepatology 1999; 29: 403–411.Direct Link:
- 39, , , , , , et al. Interleukin-6/glycoprotein 130-dependent pathways are protective during liver regeneration. J Biol Chem 2003; 278: 11281–11288.
- 40, , , , . Massive liver growth in mice induced by systemic interleukin 6 administration. Hepatology 2003; 38: 326–334.Direct Link:
- 41, , , . Stem cell factor restores hepatocyte proliferation in IL-6 knockout mice following 70% hepatectomy. J Clin Invest 2003; 112: 1407–1418.
- 42, , , , . Hepatocyte proliferation and tissue remodeling is impaired after liver injury in oncostatin M receptor knockout mice. Hepatology 2004; 39: 635–644.Direct Link:
- 43. Gut-derived endotoxin elicits hepatotrophic factor secretion for liver regeneration. Am J Physiol 1985; 249: R551–562.
- 44, , . Depressed liver regeneration after partial hepatectomy of germ-free, athymic and lipopolysaccharide-resistant mice. Hepatology 1990; 11: 916–922.Direct Link:
- 45, , , , , , et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998; 282: 2085–2088.
- 46, , . Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2001; 2: 675–680.
- 47, , , , , , et al. Contribution of Toll-like receptor/myeloid differentiation factor 88 signaling to murine liver regeneration. Hepatology 2005; 41: 443–450.Direct Link:
- 48, , , , , . Pro-inflammatory cytokine production in liver regeneration is Myd88-dependent, but independent of Cd14, Tlr2, and Tlr4. J Immunol 2006; 176(in press).
- 49, , , , , , et al. The proinflammatory mediators C3a and C5a are essential for liver regeneration. J Exp Med 2003; 198: 913–923.
- 50, , . Regulation of G1 cyclin-dependent kinases in liver regeneration. J Gastroenterol Hepatol 1998; 13( Suppl): S100–S105.
- 51, , , . Cyclin and cyclin-dependent kinase 1 mRNA expression in models of regenerating liver and human liver diseases. Am J Physiol 1993; 265: G857–G864.
- 52, , , , , . Involvement of p21 and p27 in the regulation of CDK activity and cell cycle progression in the regenerating liver. Oncogene 1998; 16: 2141–2150.
- 53
- 54, . Liver regeneration, growth factors, and amphiregulin. Gastroenterology 2005; 128: 503–506.
- 55, , , , , . Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair. Proc Natl Acad Sci U S A 2004; 101: 4477–4482.
- 56, , , , , . Met provides essential signals for liver regeneration. Proc Natl Acad Sci U S A 2004; 101: 10608–10613.
- 57, . Transforming growth factor alpha may be a physiological regulator of liver regeneration by means of an autocrine mechanism. Proc Natl Acad Sci U S A 1989; 86: 1558–1562.
- 58, , , , . Overexpression of transforming growth factor-alpha causes liver enlargement and increased hepatocyte proliferation in transgenic mice. Am J Pathol 1994; 145: 398–408.
- 59, , , , . Liver regeneration and hepatocarcinogenesis in transforming growth factor-alpha-targeted mice. Mol Carcinog 1996; 15: 183–189.Direct Link:
- 60, , , , , , et al. Role of heparin-binding epidermal growth factor-like growth factor as a hepatotrophic factor in rat liver regeneration after partial hepatectomy. Hepatology 1995; 22: 1584–1590.
- 61, , , , , , et al. Liver regeneration in heparin-binding EGF-like growth factor transgenic mice after partial hepatectomy. Gastroenterology 2003; 124: 701–707.
- 62, . The rate of incorporation of labeled thymidine into the deoxyribonucleic acid of regenerating rat liver in relation to the amount of liver excised. Cancer Res 1964; 24: 1611–1625.
- 63, , , , , , et al. Heparin-binding epidermal growth factor-like growth factor links hepatocyte priming with cell cycle progression during liver regeneration. J Biol Chem 2005; 280: 2562–2568.
- 64, , , , , , et al. Amphiregulin: an early trigger of liver regeneration in mice. Gastroenterology 2005; 128: 424–432.
- 65, , , . Diverse expression of ErbB receptor proteins during rat liver development and regeneration. Gastroenterology 2002; 123: 2017–2027.
- 66, , , , , , et al. The mitogen-activated protein kinase kinase/extracellular signal-regulated kinase cascade activation is a key signalling pathway involved in the regulation of G(1) phase progression in proliferating hepatocytes. Mol Cell Biol 1999; 19: 6003–6011.
- 67, , . Role of ERK, p38 and PI3-kinase in EGF receptor-mediated mitogenic signalling in cultured rat hepatocytes: requirement for sustained ERK activation. Cell Physiol Biochem 2003; 13: 229–238.
- 68, , , , . STAT3 contributes to the mitogenic response of hepatocytes during liver regeneration. J Biol Chem 2002; 277: 28411–28417.
- 69, , , , , . PI3K-FRAP/mTOR pathway is critical for hepatocyte proliferation whereas MEK/ERK supports both proliferation and survival. Hepatology 2002; 36: 1079–1088.Direct Link:
- 70, , , . Epidermal growth factor receptor transactivation mediates tumor necrosis factor-induced hepatocyte replication. J Biol Chem 2004; 279: 34530–34536.
- 71, , , , , . Epidermal growth factor and proliferation in rat hepatocytes in primary culture isolated at different times after partial hepatectomy. Cancer Res 1986; 46: 1318–1323.
- 72, , , , . Integral role of the EGF receptor in HGF-mediated hepatocyte proliferation. Biochem Biophys Res Commun 2002; 290: 197–203.
- 73, , , , , . Loss of cyclin D1 does not inhibit the proliferative response of mouse liver to mitogenic stimuli. Hepatology 2002; 36: 1098–1105.Direct Link:
- 74, , , , , , et al. In vivo hepatocyte proliferation is inducible through a TNF and IL-6-independent pathway. Oncogene 1998; 17: 1039–1044.
- 75, , , . Induction of replicative competence (“priming”) in normal liver. Cancer Res 1990; 50: 7023–7030.
- 76, , . Effects of protein-deprivation on the regeneration of rat liver after partial hepatectomy. Biochem J 1979; 180: 25–35.
- 77, , , , , , et al. Amino acids regulate hepatocyte proliferation through modulation of cyclin D1 expression. J Biol Chem 2003; 278: 25853–25858.
- 78, . Coordinate regulation of translation by the PI 3-kinase and mTOR pathways. Adv Cancer Res 2002; 86: 1–39.
- 79, , , , . Recent advances in the regulation of the TOR pathway by insulin and nutrients. Curr Opin Clin Nutr Metab Care 2005; 8: 67–72.
- 80, . Raptor and mTOR: subunits of a nutrient-sensitive complex. Curr Top Microbiol Immunol 2004; 279: 259–270.
- 81, , , , , , et al. Proliferation, but not growth, blocked by conditional deletion of 40S ribosomal protein S6. Science 2000; 288: 2045–2047.
- 82, , . Rapamycin-insensitive regulation of 4e-BP1 in regenerating rat liver. J Biol Chem 2001; 276: 10943–10951.
- 83, , , , , . Rapamycin-sensitive induction of eukaryotic initiation factor 4F in regenerating mouse liver. Hepatology 2004; 40: 537–544.Direct Link:
- 84, , , , , , et al. Differential regulation of extracellular matrix synthesis during liver regeneration after partial hepatectomy in rats. Hepatology 1999; 30: 1159–1166.Direct Link:
- 85, , , . Expression and activation of pro-MMP-2 and pro-MMP-9 during rat liver regeneration. Hepatology 2000; 31: 75–82.Direct Link:
- 86, , , , , , et al. Abnormal TNF activity in Timp3−/− mice leads to chronic hepatic inflammation and failure of liver regeneration. Nat Genet 2004; 36: 969–977.
- 87, , , , , , et al. TACE/ADAM17 processing of EGFR ligands indicates a role as a physiological convertase. Ann N Y Acad Sci 2003; 995: 22–38.Direct Link:
- 88, , , , , , et al. TNFalpha-mediated extracellular matrix remodeling is required for multiple division cycles in rat hepatocytes. Hepatology 2005; 41: 478–486.Direct Link:
- 89, , , , , , et al. Liver regeneration after adult living donor and deceased donor split-liver transplants. Liver Transpl 2004; 10: 374–378.Direct Link:
- 90, , , , , , et al. Liver regeneration and surgical outcome in donors of right-lobe liver grafts. Transplantation 2003; 76: 5–10.
- 91, . Hepatic progenitor cells in human liver diseases. Semin Cell Dev Biol 2002; 13: 389–396.
- 92, , , , . Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes. Am J Pathol 1997; 151: 1273–1280.

1527-3350/asset/olbannerleft.gif?v=1&s=4b2409f9534ed500d3c8da1940a23842e2b9932d)
1527-3350/asset/olbannerright.gif?v=1&s=141b9a8485298533c3e2016e937b0404f7d933e1)