| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 143, 1606-1620, Copyright © 1993 by American Society for Investigative Pathology
REGULAR ARTICLES |
MD Dabeva and DA Shafritz
Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461.
Rat liver regeneration was studied from 24 hours to 8 days after a single intraperitoneal injection of D-galactosamine (GalN). Morphological changes in the liver were analyzed in parallel with sequential changes in expression of histone-3 mRNA (a marker of cell proliferation), fetal alpha-fetoprotein (AFP) mRNA and gamma-glutamyl transpeptidase (GGT) (markers of fetal hepatocytes), and albumin mRNA and glucose-6-phosphatase (G6Pase) (markers of adult hepatocytes). Proliferation of nonparenchymal epithelial cells (NPC), detected in situ by [3H]thymidine labeling or histone-3 mRNA expression, began after 24 hours primarily in the portal area around the bile ducts. After 2 days, histone-3 labelling intensity increased in rows and clusters of NPC which expanded from the portal zone and invaded into the parenchyma. On days 3 and 5, NPC expressing his-3 mRNA expanded further, forming pseudo-ducts and islet-like structures (NPC structures). Proliferating NPC were positive for GGT. Some GGT positive cells were also positive for the fetal form of AFP mRNA, which lagged behind GGT by 24 hours and peaked on day 5. On day 3, some cells with the appearance of NPC expressed albumin mRNA. Double label in situ hybridization for fetal AFP and albumin mRNAs and dual histochemistry for GGT and G6Pase showed simultaneous expression of these markers in NPC on day 5. Other cells expressing fetal AFP mRNA or GGT on day 5 had a morphological appearance between NPC and hepatocytes (transitional cells). Proliferation of hepatocytes began on day 2, reached maximum on day 5 and then declined. Proliferating hepatocytes did not express fetal AFP mRNA or GGT. These findings indicate that after GalN injury, the liver responds by activation of progenitor cells that proliferate and then differentiate into mature hepatocytes. Adult hepatocytes can also proliferate after GAlN injury, but these hepatocytes do not undergo dedifferentiation/redifferentiation during regeneration of the hepatic lobule.
This article has been cited by other articles:
 |
|
 |
|
  K. Ishikawa, A. Sasaki, N. Haraguchi, Y. Yoshikawa, and M. Mori A Case of an {alpha}-Fetoprotein-Producing Intrahepatic Cholangiocarcinoma Suggests Probable Cancer Stem Cell Origin Oncologist, March 1, 2007; 12(3): 320 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Sangwan, G. N. Paliouras, A. Cheng, N. Dube, M. L. Tremblay, and M. Park Protein-tyrosine Phosphatase 1B Deficiency Protects against Fas-induced Hepatic Failure J. Biol. Chem., January 6, 2006; 281(1): 221 - 228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Hu, X Zhang, X Dong, L Collins, G J Sawyer, and J W Fabre A remarkable permeability of canalicular tight junctions might facilitate retrograde, non-viral gene delivery to the liver via the bile duct Gut, October 1, 2005; 54(10): 1473 - 1479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G Nowak, B-G Ericzon, S Nava, M Jaksch, M Westgren, and S Sumitran-Holgersson Identification of expandable human hepatic progenitors which differentiate into mature hepatic cells in vivo Gut, July 1, 2005; 54(7): 972 - 979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Mavier, N. Martin, D. Couchie, A.-M. Preaux, Y. Laperche, and E. S. Zafrani Expression of Stromal Cell-Derived Factor-1 and of Its Receptor CXCR4 in Liver Regeneration from Oval Cells in Rat Am. J. Pathol., December 1, 2004; 165(6): 1969 - 1977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Menthena, N. Deb, M. Oertel, P. N. Grozdanov, J. Sandhu, S. Shah, C. Guha, D. A. Shafritz, and M. D. Dabeva Bone Marrow Progenitors Are Not the Source of Expanding Oval Cells in Injured Liver Stem Cells, November 1, 2004; 22(6): 1049 - 1061. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Deane, H. Lee, J. Hamaamen, A. Ruley, M. K. Washington, B. LaFleur, S. S. Thorgeirsson, R. Price, and R. D. Beauchamp Enhanced Tumor Formation in Cyclin D1 x Transforming Growth Factor {beta}1 Double Transgenic Mice with Characterization by Magnetic Resonance Imaging Cancer Res., February 15, 2004; 64(4): 1315 - 1322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W Y Chan, F-t Chau, K K. Lee, W H Kwong, and D T Yew Substitution for natural musk in Pien Tze Huang does not affect its hepatoprotective activities Human and Experimental Toxicology, January 1, 2004; 23(1): 35 - 47. [Abstract] [PDF]
|
|
|
|
|
|
Z. He, W.-Y. Ma, G. Liu, Y. Zhang, A. M. Bode, and Z. Dong Arsenite-induced Phosphorylation of Histone H3 at Serine 10 Is Mediated by Akt1, Extracellular Signal-regulated Kinase 2, and p90 Ribosomal S6 Kinase 2 but Not Mitogen- and Stress-activated Protein Kinase 1 J. Biol. Chem., March 14, 2003; 278(12): 10588 - 10593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Braun, A. W. Thompson, and E. P. Sandgren Hepatic Microenvironment Affects Oval Cell Localization in Albumin-Urokinase-Type Plasminogen Activator Transgenic Mice Am. J. Pathol., January 1, 2003; 162(1): 195 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Asahina, H. Sato, C. Yamasaki, M. Kataoka, M. Shiokawa, S. Katayama, C. Tateno, and K. Yoshizato Pleiotrophin/Heparin-Binding Growth-Associated Molecule as a Mitogen of Rat Hepatocytes and Its Role in Regeneration and Development of Liver Am. J. Pathol., June 1, 2002; 160(6): 2191 - 2205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Sandhu, P. M. Petkov, M. D. Dabeva, and D. A. Shafritz Stem Cell Properties and Repopulation of the Rat Liver by Fetal Liver Epithelial Progenitor Cells Am. J. Pathol., October 1, 2001; 159(4): 1323 - 1334. [Abstract] [Full Text]
|
|
|
|
 |
|
 B. Knight, G. C.T. Yeoh, K. L. Husk, T. Ly, L. J. Abraham, C. Yu, J. A. Rhim, and N. Fausto Impaired Preneoplastic Changes and Liver Tumor Formation in Tumor Necrosis Factor Receptor Type 1 Knockout Mice J. Exp. Med., December 18, 2000; 192(12): 1809 - 1818. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gupta, P. Rajvanshi, H. Malhi, S. Slehria, R. P. Sokhi, S. R. G. Vasa, M. Dabeva, D. A. Shafritz, and A. Kerr Cell transplantation causes loss of gap junctions and activates GGT expression permanently in host liver Am J Physiol Gastrointest Liver Physiol, October 1, 2000; 279(4): G815 - G826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Gordon, W. B. Coleman, and J. W. Grisham Temporal Analysis of Hepatocyte Differentiation by Small Hepatocyte-Like Progenitor Cells during Liver Regeneration in Retrorsine-Exposed Rats Am. J. Pathol., September 1, 2000; 157(3): 771 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Holic, T. Suzuki, A. Corlu, D. Couchie, M. N. Chobert, C. Guguen-Guillouzo, and Y. Laperche Differential Expression of the Rat {gamma}-Glutamyl Transpeptidase Gene Promoters along with Differentiation of Hepatoblasts into Biliary or Hepatocytic Lineage Am. J. Pathol., August 1, 2000; 157(2): 537 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Braun and E. P. Sandgren Cellular Origin of Regenerating Parenchyma in a Mouse Model of Severe Hepatic Injury Am. J. Pathol., August 1, 2000; 157(2): 561 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A J STRAIN and H A CROSBY Hepatic stem cells Gut, June 1, 2000; 46(6): 743 - 745. [Full Text] [PDF]
|
|
|
|
|
|
E. Laconi Differential Growth: From Carcinogenesis to Liver Repopulation Am. J. Pathol., February 1, 2000; 156(2): 389 - 392. [Full Text] [PDF]
|
|
|
|
|
|
G. J. Gordon, W. B. Coleman, D. C. Hixson, and J. W. Grisham Liver Regeneration in Rats with Retrorsine-Induced Hepatocellular Injury Proceeds through a Novel Cellular Response Am. J. Pathol., February 1, 2000; 156(2): 607 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Cassiman, J. van Pelt, R. De Vos, F. Van Lommel, V. Desmet, S.-H. Yap, and T. Roskams Synaptophysin: A Novel Marker for Human and Rat Hepatic Stellate Cells Am. J. Pathol., December 1, 1999; 155(6): 1831 - 1839. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Lemmer, P. de la Motte Hall, N. Omori, M. Omori, E. G. Shephard, W. C.A. Gelderblom, J. P. Cruse, R. A. Barnard, W. F.O. Marasas, R. E. Kirsch, et al. Histopathology and gene expression changes in rat liver during feeding of fumonisin B1, a carcinogenic mycotoxin produced by Fusarium moniliforme Carcinogenesis, May 1, 1999; 20(5): 817 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sell Electron Microscopic Identification of Putative Liver Stem Cells and Intermediate Hepatocytes following Periportal Necrosis Induced in Rats by Allyl Alcohol Stem Cells, September 1, 1997; 15(5): 378 - 385. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. D. Dabeva, S.-G. Hwang, S. R. G. Vasa, E. Hurston, P. M. Novikoff, D. C. Hixson, S. Gupta, and D. A. Shafritz Differentiation of pancreatic epithelial progenitor cells into hepatocytes following transplantation into rat liver PNAS, July 8, 1997; 94(14): 7356 - 7361. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
