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PMID: 17559071 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Liver regeneration.

Journal of cellular physiology ·Vol. 213 ·No. 2 ·2007-11-00 ·Pages 286-300

Michalopoulos GK

Abstract

Liver regeneration after partial hepatectomy is a very complex and well-orchestrated phenomenon. It is carried out by the participation of all mature liver cell types. The process is associated with signaling cascades involving growth factors, cytokines, matrix remodeling, and several feedbacks of stimulation and inhibition of growth related signals. Liver manages to restore any lost mass and adjust its size to that of the organism, while at the same time providing full support for body homeostasis during the entire regenerative process. In situations when hepatocytes or biliary cells are blocked from regeneration, these cell types can function as facultative stem cells for each other.

MeSH Terms
Animals Epithelial Cells/metabolism Hemodynamics Hepatectomy Hepatocytes/metabolism Humans Interleukin-6/metabolism Liver/cytology,embryology,physiology Liver Regeneration/physiology Mitosis/physiology Signal Transduction/physiology Stem Cells/physiology Transforming Growth Factor beta1/metabolism
Chemicals
Interleukin-6 Transforming Growth Factor beta1
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Michalopoulos George K
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA. michalopoulosgk@upmc.edu
References (219)
219 references, click to expand
  1. Activation of hepatic stem cell compartment in the rat: role of transforming growth factor alpha, hepatocyte growth factor, and acidic fibroblast growth factor in early proliferation.
    Cell Growth Differ. 1993 Jul;4(7):555-61 PMID: 7691152
  2. Norepinephrine and neuropeptide Y promote proliferation and collagen gene expression of hepatic myofibroblastic stellate cells.
    Biochem Biophys Res Commun. 2003 Mar 21;302(4):685-90 PMID: 12646223
  3. Structural and functional characterization of the mouse hepatocyte growth factor gene promoter.
    J Biol Chem. 1994 Feb 11;269(6):4152-60 PMID: 8307976
  4. Acidic fibroblast growth factor (HBGF-1) stimulates DNA synthesis in primary rat hepatocyte cultures.
    J Cell Physiol. 1990 Apr;143(1):129-32 PMID: 1690739
  5. Multiple sites of proteolytic cleavage to release soluble forms of hepatocyte growth factor activator inhibitor type 1 from a transmembrane form.
    J Biochem. 1999 Nov;126(5):821-8 PMID: 10544273
  6. Regulation of hepatic stellate cell differentiation by the neurotrophin receptor p75NTR.
    Science. 2007 Mar 30;315(5820):1853-6 PMID: 17395831
  7. Analysis of liver regeneration in mice lacking type 1 or type 2 tumor necrosis factor receptor: requirement for type 1 but not type 2 receptor.
    Hepatology. 1998 Oct;28(4):959-70 PMID: 9755232
  8. Liver regeneration is transiently impaired in urokinase-deficient mice.
    Am J Physiol. 1998 Dec;275(6 Pt 1):G1472-9 PMID: 9843786
  9. An overview of the Notch signalling pathway.
    Semin Cell Dev Biol. 2003 Apr;14(2):113-9 PMID: 12651094
  10. IKK/NF-kappaB signaling: balancing life and death--a new approach to cancer therapy.
    J Clin Invest. 2005 Oct;115(10):2625-32 PMID: 16200195
  11. Sequestration of a hepatocyte growth factor in extracellular matrix in normal adult rat liver.
    Biochem Biophys Res Commun. 1991 Jan 15;174(1):90-5 PMID: 1824922
  12. Stability and evolution of transcriptional regulatory networks.
    Mol Syst Biol. 2006;2:2006.0021 PMID: 16738566
  13. EFFECT OF PARTIAL HEPATECTOMY ON DNA SYNTHESIS AND MITOSIS IN HETEROTOPIC PARTIAL AUTOGRAFTS OF RAT LIVER.
    Cancer Res. 1964 Sep;24:1496-501 PMID: 14221806
  14. Activation of hepatocyte growth factor by the plasminogen activators uPA and tPA.
    Am J Pathol. 1993 Sep;143(3):949-58 PMID: 8362987
  15. Role of heparin-binding epidermal growth factor-like growth factor as a hepatotrophic factor in rat liver regeneration after partial hepatectomy.
    Hepatology. 1995 Nov;22(5):1584-90 PMID: 7590679
  16. Inhibition of in vivo rat liver regeneration by 2-acetylaminofluorene affects the regulation of cell cycle-related proteins.
    Hepatology. 1998 Mar;27(3):691-6 PMID: 9500696
  17. Loss of cyclin D1 does not inhibit the proliferative response of mouse liver to mitogenic stimuli.
    Hepatology. 2002 Nov;36(5):1098-105 PMID: 12395319
  18. Morphogenetic events in mixed cultures of rat hepatocytes and nonparenchymal cells maintained in biological matrices in the presence of hepatocyte growth factor and epidermal growth factor.
    Hepatology. 1999 Jan;29(1):90-100 PMID: 9862855
  19. 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 Feb 18;94(4):1441-6 PMID: 9037072
  20. Liver regeneration 4: transcriptional control of liver regeneration.
    FASEB J. 1996 Mar;10(4):413-27 PMID: 8647340
  21. Up-regulation of telomerase in primary cultured rat hepatocytes.
    J Biochem. 1999 Aug;126(2):361-7 PMID: 10423530
  22. Morphologic and biochemical changes in dogs after portacaval shunt plus bile fistula or ileal bypass: failure of bile fistula or ileal bypass to prevent hepatocyte atrophy.
    Hepatology. 1983 Jul-Aug;3(4):581-7 PMID: 6862371
  23. Platelet-derived serotonin mediates liver regeneration.
    Science. 2006 Apr 7;312(5770):104-7 PMID: 16601191
  24. Involvement of growth factors in the regulation of pubertal mammary growth in cattle.
    Adv Exp Med Biol. 2000;480:27-43 PMID: 10959407
  25. Transforming growth factor-beta (TGF-beta) isoforms in rat liver regeneration: messenger RNA expression and activation of latent TGF-beta.
    Cell Regul. 1991 Jul;2(7):535-48 PMID: 1782214
  26. Liver stem cells.
    Mod Pathol. 1994 Jan;7(1):105-12 PMID: 8159639
  27. Hepatic expression of mature transforming growth factor beta 1 in transgenic mice results in multiple tissue lesions.
    Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2572-6 PMID: 7708687
  28. Population expansion, clonal growth, and specific differentiation patterns in primary cultures of hepatocytes induced by HGF/SF, EGF and TGF alpha in a chemically defined (HGM) medium.
    J Cell Biol. 1996 Mar;132(6):1133-49 PMID: 8601590
  29. Caveolin-1 is essential for liver regeneration.
    Science. 2006 Sep 15;313(5793):1628-32 PMID: 16973879
  30. Overexpression of transforming growth factor-alpha causes liver enlargement and increased hepatocyte proliferation in transgenic mice.
    Am J Pathol. 1994 Aug;145(2):398-408 PMID: 8053497
  31. Presence of urokinase in serum-free primary rat hepatocyte cultures and its role in activating hepatocyte growth factor.
    Cancer Res. 1996 Jun 15;56(12):2837-43 PMID: 8665523
  32. Glial fibrillary acidic protein--a cell type specific marker for Ito cells in vivo and in vitro.
    J Hepatol. 1996 Jun;24(6):719-30 PMID: 8835748
  33. Further characterization and comparison of inducible nitric oxide synthase in mouse, rat, and human hepatocytes.
    Hepatology. 1995 Jun;21(6):1552-60 PMID: 7539395
  34. Phenobarbital regulates nuclear expression of HNF-4alpha in mouse and rat hepatocytes independent of CAR and PXR.
    Hepatology. 2006 Jul;44(1):186-94 PMID: 16799975
  35. Identification of transcriptional networks during liver regeneration.
    J Biol Chem. 2005 Feb 4;280(5):3715-22 PMID: 15546871
  36. Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair.
    Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4477-82 PMID: 15070743
  37. Liver regeneration: a link to inflammation through complement.
    Adv Exp Med Biol. 2006;586:17-34 PMID: 16893062
  38. Spatiotemporal expression of angiogenesis growth factor receptors during the revascularization of regenerating rat liver.
    Hepatology. 2001 Dec;34(6):1135-48 PMID: 11732003
  39. Epidermal growth factor receptor transactivation mediates tumor necrosis factor-induced hepatocyte replication.
    J Biol Chem. 2004 Aug 13;279(33):34530-6 PMID: 15199050
  40. Hepatocyte growth factor and transforming growth factor beta1 contribute to regeneration of small-for-size liver graft immediately after transplantation.
    Transpl Int. 2003 Nov;16(11):814-9 PMID: 12879228
  41. Heparin-binding epidermal growth factor-like growth factor links hepatocyte priming with cell cycle progression during liver regeneration.
    J Biol Chem. 2005 Jan 28;280(4):2562-8 PMID: 15536070
  42. NFkappaB prevents apoptosis and liver dysfunction during liver regeneration.
    J Clin Invest. 1998 Feb 15;101(4):802-11 PMID: 9466975
  43. Activated hepatic stellate cells overexpress p75NTR after partial hepatectomy and undergo apoptosis on nerve growth factor stimulation.
    Liver Int. 2006 Jun;26(5):595-603 PMID: 16762005
  44. The processing and utilization of hepatocyte growth factor/scatter factor following partial hepatectomy in the rat.
    Hepatology. 2001 Oct;34(4 Pt 1):688-93 PMID: 11584364
  45. Six different cytokines that share GP130 as a receptor subunit, induce serum amyloid A and potentiate the induction of interleukin-6 and the activation of the hypothalamus-pituitary-adrenal axis by interleukin-1.
    Blood. 1996 Mar 1;87(5):1851-4 PMID: 8634432
  46. PDGF and signal transduction in hepatic stellate cells.
    Front Biosci. 2002 Aug 1;7:d1720-6 PMID: 12133817
  47. Peroxisomal localization of hypoxia-inducible factors and hypoxia-inducible factor regulatory hydroxylases in primary rat hepatocytes exposed to hypoxia-reoxygenation.
    Am J Pathol. 2006 Oct;169(4):1251-69 PMID: 17003483
  48. Amnion-derived pluripotent/multipotent stem cells.
    Stem Cell Rev. 2006;2(2):133-42 PMID: 17237552
  49. Adrenergic effects on secretion of epidermal growth factor from Brunner's glands.
    Gut. 1985 Sep;26(9):920-7 PMID: 2863199
  50. The proinflammatory mediators C3a and C5a are essential for liver regeneration.
    J Exp Med. 2003 Sep 15;198(6):913-23 PMID: 12975457
  51. Long-term, near-total liver replacement by transplantation of isolated hepatocytes in rats treated with retrorsine.
    Am J Pathol. 1998 Jul;153(1):319-29 PMID: 9665494
  52. The physiology of transforming growth factor-alpha.
    Adv Cancer Res. 1992;58:27-52 PMID: 1546559
  53. Induction of DNA synthesis in cultured rat hepatocytes through stimulation of alpha 1 adrenoreceptor by norepinephrine.
    Science. 1985 Feb 15;227(4688):749-51 PMID: 2982212
  54. TACE/ADAM17 processing of EGFR ligands indicates a role as a physiological convertase.
    Ann N Y Acad Sci. 2003 May;995:22-38 PMID: 12814936
  55. Scatter factor/hepatocyte growth factor is essential for liver development.
    Nature. 1995 Feb 23;373(6516):699-702 PMID: 7854452
  56. Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver.
    Nature. 2007 Feb 22;445(7130):886-91 PMID: 17259975
  57. Expression of stem cell factor and its receptor, c-kit, during liver regeneration from putative stem cells in adult rat.
    Lab Invest. 1994 Apr;70(4):511-6 PMID: 7513770
  58. Tumor necrosis factor primes hepatocytes for DNA replication in the rat.
    Hepatology. 1998 Nov;28(5):1226-34 PMID: 9794905
  59. Liver regeneration, growth factors, and amphiregulin.
    Gastroenterology. 2005 Feb;128(2):503-6 PMID: 15685562
  60. Transforming growth factor-alpha (TGF alpha) concentrations increase in regenerating rat liver: evidence for a delayed accumulation of mature TGF alpha.
    Endocrinology. 1993 Oct;133(4):1731-8 PMID: 8404616
  61. Notch signaling: from the outside in.
    Dev Biol. 2000 Dec 15;228(2):151-65 PMID: 11112321
  62. Growth factor-regulated pathways in epithelial cell proliferation.
    Am Rev Respir Dis. 1990 Dec;142(6 Pt 2):S7-10 PMID: 2252277
  63. Proteoglycan gene expression in rat liver after partial hepatectomy.
    Biochem Biophys Res Commun. 1996 Nov 21;228(3):690-4 PMID: 8941340
  64. Regeneration of rat liver: transfer of humoral agent by cross circulation.
    Science. 1967 Oct 13;158(3798):272-4 PMID: 6053886
  65. Activin induces hepatocyte cell growth arrest through induction of the cyclin-dependent kinase inhibitor p15INK4B and Sp1.
    Cell Signal. 2004 Jun;16(6):693-701 PMID: 15093610
  66. Liver regeneration.
    Adv Biochem Eng Biotechnol. 2005;93:101-34 PMID: 15791946
  67. Hepatocellular expression of glutamine synthetase: an indicator of morphogen actions as master regulators of zonation in adult liver.
    Prog Histochem Cytochem. 2007;41(4):201-66 PMID: 17368308
  68. TGF-beta: regulation of extracellular matrix.
    Kidney Int. 1992 Mar;41(3):557-9 PMID: 1573828
  69. Cytotoxicity of TNFalpha is regulated by integrin-mediated matrix signaling.
    EMBO J. 2007 Mar 7;26(5):1257-67 PMID: 17318182
  70. To regeneration...with complement.
    Adv Exp Med Biol. 2006;586:63-70 PMID: 16893065
  71. Tumor necrosis factor induces DNA replication in hepatic cells through nuclear factor kappaB activation.
    Cell Growth Differ. 1999 Dec;10(12):819-28 PMID: 10616907
  72. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo.
    Nat Med. 2000 Nov;6(11):1229-34 PMID: 11062533
  73. Extracellular matrix remodeling at the early stages of liver regeneration in the rat.
    Hepatology. 1997 Oct;26(4):896-904 PMID: 9328311
  74. Intact signaling by transforming growth factor beta is not required for termination of liver regeneration in mice.
    Hepatology. 2004 Nov;40(5):1098-105 PMID: 15389868
  75. Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-MET.
    Oncogene. 1991 Apr;6(4):501-4 PMID: 1827664
  76. Impaired liver regeneration in inducible nitric oxide synthasedeficient mice.
    Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13829-34 PMID: 9811886
  77. Biphasic effect of transforming growth factor-beta 1 on in vitro angiogenesis.
    Exp Cell Res. 1993 Feb;204(2):356-63 PMID: 7679998
  78. Disruption of hepatic adipogenesis is associated with impaired liver regeneration in mice.
    Hepatology. 2004 Dec;40(6):1322-32 PMID: 15565660
  79. Gene regulation by interleukin 6.
    Biochimie. 1991 Jan;73(1):47-50 PMID: 2031958
  80. Peroxisome proliferator-induced pleiotropic responses: pursuit of a phenomenon.
    Ann N Y Acad Sci. 1996 Dec 27;804:176-201 PMID: 8993544
  81. Mitosis and apoptosis in the liver of interleukin-6-deficient mice after partial hepatectomy.
    Hepatology. 1999 Feb;29(2):403-11 PMID: 9918916
  82. Control of hepatocyte replication by two serum factors.
    Cancer Res. 1984 Oct;44(10):4414-9 PMID: 6235912
  83. Met provides essential signals for liver regeneration.
    Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10608-13 PMID: 15249655
  84. Cell-extracellular matrix interactions can regulate the switch between growth and differentiation in rat hepatocytes: reciprocal expression of C/EBP alpha and immediate-early growth response transcription factors.
    Mol Cell Biol. 1994 Sep;14(9):5858-69 PMID: 8065319
  85. Expression of hepatic transcription factors during liver development and oval cell differentiation.
    J Cell Biol. 1994 Jul;126(1):223-33 PMID: 8027180
  86. Antibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy.
    Am J Physiol. 1992 Oct;263(4 Pt 1):G579-85 PMID: 1415718
  87. A potential role of somatostatin and its receptor SSTR4 in the migration of hepatic oval cells.
    Lab Invest. 2006 May;86(5):477-89 PMID: 16534498
  88. Normal liver regeneration in p50/nuclear factor kappaB1 knockout mice.
    Hepatology. 2001 Apr;33(4):915-24 PMID: 11283856
  89. Histochemical changes in livers from portacaval-shunted rats.
    J Natl Cancer Inst. 1986 Apr;76(4):731-8 PMID: 2421039
  90. Transforming growth factor beta and activin tonically inhibit DNA synthesis in the rat liver.
    Hepatology. 2001 Nov;34(5):918-25 PMID: 11679962
  91. Propagation of adult rat bone marrow-derived hepatocyte-like cells by serial passages in vitro.
    Cell Transplant. 2004;13(4):385-91 PMID: 15468680
  92. Growth factor signal transduction immediately after two-thirds partial hepatectomy in the rat.
    Cancer Res. 1999 Aug 15;59(16):3954-60 PMID: 10463591
  93. Defective hepatic regeneration after partial hepatectomy in leptin-deficient mice is not rescued by exogenous leptin.
    Lab Invest. 2006 Nov;86(11):1161-71 PMID: 16983330
  94. Insulin, glucagon, and the liver.
    Adv Enzyme Regul. 1976;15:221-30 PMID: 1030184
  95. Increased expression of c-fos, c-jun and LRF-1 is not required for in vivo priming of hepatocytes by the mitogen TCPOBOP.
    Oncogene. 1997 Feb 20;14(7):857-63 PMID: 9047393
  96. HGF: a multifunctional growth factor controlling cell scattering.
    Int J Biochem Cell Biol. 1999 Dec;31(12):1357-62 PMID: 10641789
  97. Distribution and activity of glutamine synthase and carbamoylphosphate synthase upon enlargement of the liver lobule by repeated partial hepatectomies.
    J Hepatol. 1993 Mar;17(3):397-407 PMID: 8100248
  98. Effect of portal hemodynamics on liver regeneration studied in a novel portohepatic shunt rat model.
    Surgery. 2004 Nov;136(5):1028-37 PMID: 15523397
  99. VEGF isoforms and receptors expression throughout acute acetaminophen-induced liver injury and regeneration.
    Arch Toxicol. 2007 Oct;81(10):729-41 PMID: 17431590
  100. The initiation of liver development is dependent on Foxa transcription factors.
    Nature. 2005 Jun 16;435(7044):944-7 PMID: 15959514
  101. Triidothyronine: on its role as a specific hepatomitogen.
    Cytobios. 1980;28(111-112):165-77 PMID: 7214999
  102. c-Met is essential for wound healing in the skin.
    J Cell Biol. 2007 Apr 9;177(1):151-62 PMID: 17403932
  103. Gadd45beta is induced through a CAR-dependent, TNF-independent pathway in murine liver hyperplasia.
    Hepatology. 2005 Nov;42(5):1118-26 PMID: 16231353
  104. Matrix metalloproteinase-9 is an important factor in hepatic regeneration after partial hepatectomy in mice.
    Hepatology. 2006 Sep;44(3):540-9 PMID: 16941692
  105. Expression of Notch-1 and its ligand Jagged-1 in rat liver during liver regeneration.
    Hepatology. 2004 Apr;39(4):1056-65 PMID: 15057910
  106. Liver regeneration.
    Science. 1997 Apr 4;276(5309):60-6 PMID: 9082986
  107. Stimulation of DNA synthesis in hepatocytes by hepatocyte growth factor bound to extracellular matrix.
    Biochem Biophys Res Commun. 1993 Mar 31;191(3):1218-23 PMID: 8466499
  108. The role of activin and transforming growth factor-beta in the regulation of organ mass in the rat liver.
    Hepatology. 2000 Apr;31(4):916-21 PMID: 10733548
  109. Evidence that cyclin D1 mediates both growth and proliferation downstream of TOR in hepatocytes.
    J Biol Chem. 2003 Feb 7;278(6):3656-63 PMID: 12446670
  110. Impaired liver regeneration after partial hepatectomy in db/db mice.
    Exp Toxicol Pathol. 2003 Mar;54(4):281-6 PMID: 12710710
  111. STAT-3 overexpression and p21 up-regulation accompany impaired regeneration of fatty livers.
    Am J Pathol. 2002 Jul;161(1):155-61 PMID: 12107100
  112. The role of Ito cells in the biosynthesis of HGF-SF in the liver.
    EXS. 1993;65:285-99 PMID: 8380738
  113. Interleukin-6, hepatocyte growth factor, and their receptors in biliary epithelial cells during a type I ductular reaction in mice: interactions between the periductal inflammatory and stromal cells and the biliary epithelium.
    Hepatology. 1998 Nov;28(5):1260-8 PMID: 9794910
  114. Collagenase pretreatment and the mitogenic effects of hepatocyte growth factor and transforming growth factor-alpha in adult rat liver.
    Hepatology. 1994 Jun;19(6):1521-7 PMID: 8188184
  115. Hepatocyte growth factor, blood clearance, organ uptake, and biliary excretion in normal and partially hepatectomized rats.
    Lab Invest. 1993 Mar;68(3):270-6 PMID: 8450646
  116. Amphiregulin: an early trigger of liver regeneration in mice.
    Gastroenterology. 2005 Feb;128(2):424-32 PMID: 15685553
  117. Hepatocyte growth factor induces hepatocyte proliferation in vivo and allows for efficient retroviral-mediated gene transfer in mice.
    Hepatology. 1998 Sep;28(3):707-16 PMID: 9731563
  118. Adrenergic stimulation of hepatocyte growth factor expression.
    Biochem Biophys Res Commun. 1999 Aug 19;262(1):76-9 PMID: 10448071
  119. Hepatic peroxisome proliferation: induction by BR-931, a hypolipidemic analog of WY-14,643.
    Arch Int Pharmacodyn Ther. 1978 Jul;234(1):4-14 PMID: 708142
  120. Expression of growth factors and growth factor receptor in non-healing and healing ischaemic ulceration.
    Eur J Vasc Endovasc Surg. 2006 May;31(5):516-22 PMID: 16427789
  121. Lung may have an endocrine function producing hepatocyte growth factor in response to injury of distal organs.
    Biochem Biophys Res Commun. 1992 Jan 31;182(2):802-9 PMID: 1531175
  122. Rapid DNA binding by nuclear factor kappa B in hepatocytes at the start of liver regeneration.
    Cell Growth Differ. 1995 Apr;6(4):417-27 PMID: 7794809
  123. Liver regeneration versus direct hyperplasia.
    FASEB J. 1996 Aug;10(10):1118-28 PMID: 8751714
  124. Hepatic transdifferentiation in the pancreas.
    Semin Cell Biol. 1995 Jun;6(3):151-6 PMID: 7548854
  125. TGF-beta is a potent inhibitor of hepatocyte growth factor secretion by human fibroblasts.
    Cell Biol Int Rep. 1992 Sep;16(9):917-26 PMID: 1423659
  126. Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice.
    Science. 1996 Nov 22;274(5291):1379-83 PMID: 8910279
  127. Cross-talk between epidermal growth factor receptor and c-Met signal pathways in transformed cells.
    J Biol Chem. 2000 Mar 24;275(12):8806-11 PMID: 10722725
  128. Inducible inactivation of Notch1 causes nodular regenerative hyperplasia in mice.
    Hepatology. 2005 Mar;41(3):487-96 PMID: 15723439
  129. Angiogenesis-independent endothelial protection of liver: role of VEGFR-1.
    Science. 2003 Feb 7;299(5608):890-3 PMID: 12574630
  130. Hepatocyte nuclear factor 4alpha orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver.
    Proc Natl Acad Sci U S A. 2006 May 30;103(22):8419-24 PMID: 16714383
  131. STAT3 contributes to the mitogenic response of hepatocytes during liver regeneration.
    J Biol Chem. 2002 Aug 9;277(32):28411-7 PMID: 12032149
  132. Hepatocyte growth factor induces Wnt-independent nuclear translocation of beta-catenin after Met-beta-catenin dissociation in hepatocytes.
    Cancer Res. 2002 Apr 1;62(7):2064-71 PMID: 11929826
  133. Cell cycle effects resulting from inhibition of hepatocyte growth factor and its receptor c-Met in regenerating rat livers by RNA interference.
    Hepatology. 2007 Jun;45(6):1471-7 PMID: 17427161
  134. Kinetics of hepatocellular proliferation as a function of the microvascular structure and functional state of the liver.
    Ciba Found Symp. 1977;(55):31-53 PMID: 248005
  135. Human and rat hepatic stellate cells express neurotrophins and neurotrophin receptors.
    Hepatology. 2001 Jan;33(1):148-58 PMID: 11124831
  136. Growth stimulation followed by growth inhibition in livers of female rats treated with ethinyl estradiol.
    Carcinogenesis. 1994 Oct;15(10):2117-23 PMID: 7955042
  137. Alpha 1-adrenergic effects and liver regeneration.
    Hepatology. 1987 Nov-Dec;7(6):1189-94 PMID: 2824312
  138. Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes.
    Am J Pathol. 1997 Nov;151(5):1273-80 PMID: 9358753
  139. In vivo differentiation of rat liver oval cells into hepatocytes.
    Cancer Res. 1989 Mar 15;49(6):1541-7 PMID: 2466557
  140. Liver cell proliferation induced by nafenopin and cyproterone acetate is not associated with increases in activation of transcription factors NF-kappaB and AP-1 or with expression of tumor necrosis factor alpha.
    Hepatology. 1997 Mar;25(3):585-92 PMID: 9049203
  141. Precursor-product relationship between oval cells and hepatocytes: comparison between tritiated thymidine and bromodeoxyuridine as tracers.
    Carcinogenesis. 1996 Oct;17(10):2143-51 PMID: 8895481
  142. Integrin-linked kinase is involved in matrix-induced hepatocyte differentiation.
    Biochem Biophys Res Commun. 2007 Feb 16;353(3):638-43 PMID: 17194454
  143. Signaling pathways and genes that inhibit pathogen-induced macrophage apoptosis--CREB and NF-kappaB as key regulators.
    Immunity. 2005 Sep;23(3):319-29 PMID: 16169504
  144. Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital.
    Mol Pharmacol. 2002 Jan;61(1):1-6 PMID: 11752199
  145. Cell fusion is the principal source of bone-marrow-derived hepatocytes.
    Nature. 2003 Apr 24;422(6934):897-901 PMID: 12665832
  146. Lessons from animal models of NASH.
    Hepatol Res. 2005 Oct;33(2):138-44 PMID: 16198624
  147. Insulin, glucagon, liver regeneration, and DNA synthesis.
    Metabolism. 1976 Nov;25(11 Suppl 1):1423-5 PMID: 979645
  148. Rescue of embryonic lethality in hepatocyte growth factor/scatter factor knockout mice.
    Genesis. 2000 Jul;27(3):99-103 PMID: 10951502
  149. Oval cell response in 2-acetylaminofluorene/partial hepatectomy rat is attenuated by short interfering RNA targeted to stromal cell-derived factor-1.
    Am J Pathol. 2006 Dec;169(6):2066-74 PMID: 17148669
  150. Production of interleukin 6 by hepatoma cells.
    Mol Biol Med. 1990 Jun;7(3):273-85 PMID: 1699111
  151. Influence of epidermal growth factor on liver regeneration after partial hepatectomy in rats.
    Hepatology. 1988 Sep-Oct;8(5):992-6 PMID: 3047041
  152. Bone marrow as a potential source of hepatic oval cells.
    Science. 1999 May 14;284(5417):1168-70 PMID: 10325227
  153. Effects of partial hepatectomy on transplanted hepatocytes.
    Cancer Res. 1982 Aug;42(8):3000-4 PMID: 7046913
  154. Expression and activation of pro-MMP-2 and pro-MMP-9 during rat liver regeneration.
    Hepatology. 2000 Jan;31(1):75-82 PMID: 10613731
  155. Changes in WNT/beta-catenin pathway during regulated growth in rat liver regeneration.
    Hepatology. 2001 May;33(5):1098-109 PMID: 11343237
  156. Immediate early detection of urokinase receptor after partial hepatectomy and its implications for initiation of liver regeneration.
    Hepatology. 1995 Jun;21(6):1695-701 PMID: 7768515
  157. Expression of hepatocyte growth factor mRNA in regenerating rat liver after partial hepatectomy.
    Biochem Biophys Res Commun. 1991 May 31;177(1):559-65 PMID: 1828343
  158. Emerging multipotent aspects of hepatocyte growth factor.
    J Biochem. 1996 Apr;119(4):591-600 PMID: 8743556
  159. Down-regulation of transforming growth factor beta receptor type I, II, and III during liver regeneration.
    Am J Surg. 1995 Jan;169(1):126-31; discussion 131-2 PMID: 7817981
  160. Bile ductular damage induced by methylene dianiline inhibits oval cell activation.
    Am J Pathol. 1997 Oct;151(4):905-9 PMID: 9327722
  161. Transcriptional control of wound repair.
    Annu Rev Cell Dev Biol. 2007;23:69-92 PMID: 17474876
  162. Altered responses of regenerating hepatocytes to norepinephrine and transforming growth factor type beta.
    J Cell Physiol. 1989 Dec;141(3):503-9 PMID: 2574179
  163. Liver regeneration in heparin-binding EGF-like growth factor transgenic mice after partial hepatectomy.
    Gastroenterology. 2003 Mar;124(3):701-7 PMID: 12612909
  164. Transcriptional regulatory signals define cytokine-dependent and -independent pathways in liver regeneration.
    Semin Liver Dis. 1999;19(2):117-27 PMID: 10422195
  165. Epidermal growth factor secreted from the salivary gland is necessary for liver regeneration.
    Am J Physiol. 1995 May;268(5 Pt 1):G872-8 PMID: 7762671
  166. Metalloproteinase inhibitor TIMP-1 affects hepatocyte cell cycle via HGF activation in murine liver regeneration.
    Hepatology. 2005 Apr;41(4):857-67 PMID: 15726641
  167. Role of connective tissue growth factor in oval cell response during liver regeneration after 2-AAF/PHx in rats.
    Gastroenterology. 2005 Jun;128(7):2077-88 PMID: 15940639
  168. Liver regeneration: from myth to mechanism.
    Nat Rev Mol Cell Biol. 2004 Oct;5(10):836-47 PMID: 15459664
  169. Induction of cyclin D1 transcription and CDK2 activity by Notch(ic): implication for cell cycle disruption in transformation by Notch(ic).
    Mol Cell Biol. 2001 Sep;21(17):5925-34 PMID: 11486031
  170. Differential regulation of extracellular matrix synthesis during liver regeneration after partial hepatectomy in rats.
    Hepatology. 1999 Nov;30(5):1159-66 PMID: 10534336
  171. The role of SF/HGF and c-Met in the development of skeletal muscle.
    Development. 1999 Apr;126(8):1621-9 PMID: 10079225
  172. Small proline-rich proteins 2 are noncoordinately upregulated by IL-6/STAT3 signaling after bile duct ligation.
    Lab Invest. 2005 Jan;85(1):109-23 PMID: 15558059
  173. Role of fibroblast growth factor type 1 and 2 in carbon tetrachloride-induced hepatic injury and fibrogenesis.
    Am J Pathol. 2003 Oct;163(4):1653-62 PMID: 14507672
  174. Differential regulation of urokinase-type plasminogen activator expression by fluid shear stress in human coronary artery endothelial cells.
    Am J Physiol Heart Circ Physiol. 2004 Nov;287(5):H2027-34 PMID: 15231498
  175. Hormonal factors concerned with liver regeneration.
    Ciba Found Symp. 1977;(55):95-107 PMID: 306914
  176. Sinusoidal endothelial cell proliferation and expression of angiopoietin/Tie family in regenerating rat liver.
    J Hepatol. 2001 May;34(5):690-8 PMID: 11434615
  177. Orthogonal analysis of C/EBPbeta targets in vivo during liver proliferation.
    Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):12986-91 PMID: 15317935
  178. Type beta transforming growth factor reversibly inhibits the early proliferative response to partial hepatectomy in the rat.
    Proc Natl Acad Sci U S A. 1988 Jul;85(14):5126-30 PMID: 3164865
  179. Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration.
    Science. 2006 Apr 14;312(5771):233-6 PMID: 16614213
  180. The mitogenic activity of hepatocyte growth factor on rat hepatocytes is dependent upon endogenous transforming growth factor-alpha.
    Am J Pathol. 2000 Nov;157(5):1693-701 PMID: 11073828
  181. Liver regeneration.
    Hepatology. 2006 Feb;43(2 Suppl 1):S45-53 PMID: 16447274
  182. Liver regeneration and hepatocarcinogenesis in transforming growth factor-alpha-targeted mice.
    Mol Carcinog. 1996 Mar;15(3):183-9 PMID: 8597531
  183. Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells.
    Hepatology. 2004 Jun;39(6):1477-87 PMID: 15185286
  184. 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 Mar;86(5):1558-62 PMID: 2922399
  185. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion.
    Nature. 2002 Apr 4;416(6880):542-5 PMID: 11932747
  186. Hepatocyte growth factor (hepatopoietin A) rapidly increases in plasma before DNA synthesis and liver regeneration stimulated by partial hepatectomy and carbon tetrachloride administration.
    Hepatology. 1991 Apr;13(4):743-50 PMID: 1826282
  187. Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver.
    EMBO J. 1998 Oct 1;17(19):5588-97 PMID: 9755159
  188. Cell proliferation induced by triiodothyronine in rat liver is associated with nodule regression and reduction of hepatocellular carcinomas.
    Cancer Res. 2000 Feb 1;60(3):603-9 PMID: 10676643
  189. Epidermal growth factor (EGF)-like repeats of human tenascin-C as ligands for EGF receptor.
    J Cell Biol. 2001 Jul 23;154(2):459-68 PMID: 11470832
  190. Activated rat stellate cells express c-met and respond to hepatocyte growth factor to enhance transforming growth factor beta1 expression and DNA synthesis.
    Biochem Biophys Res Commun. 1998 Sep 29;250(3):769-75 PMID: 9784421
  191. Regulation of IL-6 and the hepatic IL-6 receptor in acute inflammation in vivo.
    Cytokine. 1993 Jan;5(1):1-7 PMID: 7683503
  192. Interleukin 6/gp130-dependent pathways are protective during chronic liver diseases.
    Hepatology. 2003 Jul;38(1):218-29 PMID: 12830005
  193. Baboon-to-human liver transplantation.
    Lancet. 1993 Jan 9;341(8837):65-71 PMID: 8093402
  194. [Capacity of regeneration in liver epithelia of juvenile, repeated partially hepatectomized rats. Autoradiographic studies after continous infusion of 3H-thymidine (author's transl)].
    Virchows Arch B Cell Pathol. 1973 Nov 28;14(2):93-103 PMID: 4203888
  195. Loss of integrin linked kinase from mouse hepatocytes in vitro and in vivo results in apoptosis and hepatitis.
    Hepatology. 2007 Apr;45(4):1025-34 PMID: 17385211
  196. Impaired hepatocyte DNA synthetic response posthepatectomy in insulin-like growth factor binding protein 1-deficient mice with defects in C/EBP beta and mitogen-activated protein kinase/extracellular signal-regulated kinase regulation.
    Mol Cell Biol. 2003 Feb;23(4):1251-9 PMID: 12556485
  197. Biliary wound healing, ductular reactions, and IL-6/gp130 signaling in the development of liver disease.
    World J Gastroenterol. 2006 Jun 14;12(22):3512-22 PMID: 16773708
  198. Regulation and significance of hepatocyte-derived matrix metalloproteinases in liver remodeling.
    Biochem Biophys Res Commun. 2000 Jun 16;272(3):681-6 PMID: 10860814
  199. Senescence, wound healing and cancer: the PAI-1 connection.
    Cell Cycle. 2006 Dec;5(23):2697-703 PMID: 17172853
  200. Update on hepatic stem cells.
    Liver. 2001 Dec;21(6):367-73 PMID: 11903879
  201. Liver regeneration.
    J Hepatol. 2000;32(1 Suppl):19-31 PMID: 10728791
  202. Deficient liver regeneration after carbon tetrachloride injury in mice lacking type 1 but not type 2 tumor necrosis factor receptor.
    Am J Pathol. 1998 Jun;152(6):1577-89 PMID: 9626061
  203. Immunolocalization of putative human liver progenitor cells in livers from patients with end-stage primary biliary cirrhosis and sclerosing cholangitis using the monoclonal antibody OV-6.
    Am J Pathol. 1998 Mar;152(3):771-9 PMID: 9502419
  204. Thinking outside the cell: proteases regulate hepatocyte division.
    Trends Cell Biol. 2005 Oct;15(10):555-63 PMID: 16150595
  205. Transdifferentiation of rat hepatocytes into biliary cells after bile duct ligation and toxic biliary injury.
    Hepatology. 2005 Mar;41(3):535-44 PMID: 15726663
  206. Comitogenic effects of estrogens on DNA synthesis induced by various growth factors in cultured female rat hepatocytes.
    Hepatology. 1994 Jan;19(1):183-92 PMID: 7506224
  207. Disruption of redox homeostasis in tumor necrosis factor-induced apoptosis in a murine hepatocyte cell line.
    Am J Pathol. 2000 Jul;157(1):221-36 PMID: 10880392
  208. The IKK NF-kappa B system: a treasure trove for drug development.
    Nat Rev Drug Discov. 2004 Jan;3(1):17-26 PMID: 14708018
  209. Norepinephrine modulates the growth-inhibitory effect of transforming growth factor-beta in primary rat hepatocyte cultures.
    J Cell Physiol. 1988 Jun;135(3):551-5 PMID: 3165094
  210. Bone marrow-derived hepatic oval cells differentiate into hepatocytes in 2-acetylaminofluorene/partial hepatectomy-induced liver regeneration.
    Gastroenterology. 2007 Mar;132(3):1077-87 PMID: 17383429
  211. A mechanism of cell survival: sequestration of Fas by the HGF receptor Met.
    Mol Cell. 2002 Feb;9(2):411-21 PMID: 11864613
  212. Histological organization in hepatocyte organoid cultures.
    Am J Pathol. 2001 Nov;159(5):1877-87 PMID: 11696448
  213. Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas.
    Hepatology. 2006 Oct;44(4):1012-24 PMID: 17006932
  214. Modulation of insulin-like growth factor-II/mannose 6-phosphate receptors and transforming growth factor-beta 1 during liver regeneration.
    J Biol Chem. 1991 Nov 25;266(33):22444-50 PMID: 1718994
  215. TGF-beta1, -beta2 and -beta3 cooperate to facilitate tubulogenesis in the explanted quail heart.
    J Vasc Res. 2004 Nov-Dec;41(6):491-8 PMID: 15528931
  216. Multiple levels of Notch signal regulation (review).
    Mol Membr Biol. 2002 Jan-Mar;19(1):27-38 PMID: 11989820
  217. An alpha 2-macroglobulin receptor-dependent mechanism for the plasma clearance of transforming growth factor-beta 1 in mice.
    J Clin Invest. 1991 Jan;87(1):39-44 PMID: 1702100
  218. Vascular endothelial growth factor and angiopoietins regulate sinusoidal regeneration and remodeling after partial hepatectomy in rats.
    World J Gastroenterol. 2005 Dec 14;11(46):7254-60 PMID: 16437624
  219. Rapid activation of the Stat3 transcription complex in liver regeneration.
    Hepatology. 1995 May;21(5):1443-9 PMID: 7737651
Article Info
Journal
Journal of cellular physiology
Abbr.
J Cell Physiol
ISSN
0021-9541
DOI
10.1002/jcp.21172
Email
michalopoulosgk@upmc.edu
Published
2007-11-00
Pages
286-300
Language
English
Region
United States
NLM ID
0050222
PMCID
PMC2701258
Subset
IM
Grants
NCATS NIH HHS · UL1 TR000005 · United States
NCI NIH HHS · R01 CA103958-05 · United States
NCI NIH HHS · R01 CA103958 · United States
NCI NIH HHS · CA035373 · United States
NCI NIH HHS · CA103958 · United States
NCI NIH HHS · R01 CA035373 · United States
NCI NIH HHS · R01 CA035373-24 · United States
External Links
PubMed source DOI: 10.1002/jcp.21172 PMC Full Text View journal details
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