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Science 4 April 1997:
Vol. 276. no. 5309, pp. 60 - 66
DOI: 10.1126/science.276.5309.60
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Articles

Liver Regeneration

George K. Michalopoulos * and Marie C. DeFrances

Liver regeneration after the loss of hepatic tissue is a fundamental parameter of liver response to injury. Recognized as a phenomenon from mythological times, it is now defined as an orchestrated response induced by specific external stimuli and involving sequential changes in gene expression, growth factor production, and morphologic structure. Many growth factors and cytokines, most notably hepatocyte growth factor, epidermal growth factor, transforming growth factor-alpha , interleukin-6, tumor necrosis factor-alpha , insulin, and norepinephrine, appear to play important roles in this process. This review attempts to integrate the findings of the last three decades and looks toward clues as to the nature of the causes that trigger this fascinating organ and cellular response.

The authors are in the Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
*   To whom correspondence should be addressed.

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Experimental Biology and Medicine 230, 61-67
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Somatic deletion events occur during early embryonic development and modify the extent of CAG expansion in subsequent generations.
I.V. Kovtun, A.R. Thornhill, and C.T. McMurray (2004)
Hum. Mol. Genet. 13, 3057-3068
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Gene transfer of hepatocyte growth factor with prostacyclin synthase in severe pulmonary hypertension of rats.
M. Ono, Y. Sawa, N. Fukushima, H. Suhara, T. Nakamura, C. Yokoyama, T. Tanabe, and H. Matsuda (2004)
Eur. J. Cardiothorac. Surg. 26, 1092-1097
   Abstract »    Full Text »    PDF »
Organ Slice Viability Extended for Pathway Characterization: An in Vitro Model to Investigate Fibrosis.
A. E. M. Vickers, M. Saulnier, E. Cruz, M. T. Merema, K. Rose, P. Bentley, and P. Olinga (2004)
Toxicol. Sci. 82, 534-544
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Inhibition of rat liver regeneration after partial hepatectomy and induction of ERK phosphorylation by Cpd 5, a K vitamin-based anticancer compound.
S. Kar, M. Wang, K. S. Rosi, C. S. Wilcox, and B. I. Carr (2004)
Carcinogenesis 25, 2345-2351
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Hepatocyte Growth Factor Suppresses Vascular Medial Hyperplasia and Matrix Accumulation in Advanced Pulmonary Hypertension of Rats.
M. Ono, Y. Sawa, S. Mizuno, N. Fukushima, H. Ichikawa, K. Bessho, T. Nakamura, and H. Matsuda (2004)
Circulation 110, 2896-2902
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Induction of hepatocyte proliferation by retinoic acid.
G.M. Ledda-Columbano, M. Pibiri, F. Molotzu, C. Cossu, L. Sanna, G. Simbula, A. Perra, and A. Columbano (2004)
Carcinogenesis 25, 2061-2066
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Histone H4 histidine kinase displays the expression pattern of a liver oncodevelopmental marker.
E. Tan, P. G. Besant, X. L. Zu, C. W. Turck, M. A. Bogoyevitch, S. G. Lim, P. V. Attwood, and G. C. Yeoh (2004)
Carcinogenesis 25, 2083-2088
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Delayed Hepatocellular Mitotic Progression and Impaired Liver Regeneration in Early Growth Response-1-deficient Mice.
Y. Liao, O. N. Shikapwashya, E. Shteyer, B. K. Dieckgraefe, P. W. Hruz, and D. A. Rudnick (2004)
J. Biol. Chem. 279, 43107-43116
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Clock Genes in Cell Clocks: Roles, Actions, and Mysteries.
H. Okamura (2004)
J Biol Rhythms 19, 388-399
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Role of Growth Hormone (GH) in Liver Regeneration.
P. A. Pennisi, J. J. Kopchick, S. Thorgeirsson, D. LeRoith, and S. Yakar (2004)
Endocrinology 145, 4748-4755
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Patterns of Gene Expression Reveal a Temporally Orchestrated Wound Healing Response in the Injured Spinal Cord.
M. J. Velardo, C. Burger, P. R. Williams, H. V. Baker, M. C. Lopez, T. H. Mareci, T. E. White, N. Muzyczka, and P. J. Reier (2004)
J. Neurosci. 24, 8562-8576
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Genetic Basis of Cancer of the Kidney: Disease-Specific Approaches to Therapy.
W. M. Linehan, J. Vasselli, R. Srinivasan, M. M. Walther, M. Merino, P. Choyke, C. Vocke, L. Schmidt, J. S. Isaacs, G. Glenn, et al. (2004)
Clin. Cancer Res. 10, 6282S-6289S
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Expression of a Functional C5a Receptor in Regenerating Hepatocytes and Its Involvement in a Proliferative Signaling Pathway in Rat.
M. Daveau, M. Benard, M. Scotte, M.-T. Schouft, M. Hiron, A. Francois, J.-P. Salier, and M. Fontaine (2004)
J. Immunol. 173, 3418-3424
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Progression or Resolution of Coxsackievirus B4-Induced Pancreatitis: a Genomic Analysis.
S. E. Ostrowski, A. A. Reilly, D. N. Collins, and A. I. Ramsingh (2004)
J. Virol. 78, 8229-8237
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