| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 148, 785-800, Copyright © 1996 by American Society for Investigative Pathology
REGULAR ARTICLES |
M Pinzani, S Milani, H Herbst, R DeFranco, C Grappone, A Gentilini, A Caligiuri, G Pellegrini, DV Ngo, RG Romanelli and P Gentilini
Istituto di Medicina Interna-Centro Interuniversitario di Fisiopatologia Epatica, Universita di Firenze, Italy.
Expression of platelet-derived growth factor (PDGF) and its receptor (R) subunits was evaluated in normal human liver and in cirrhotic liver tissue by in situ hybridization and immunohistochemistry. In normal liver, PDGF and PDGF-R subunit expression was limited to a few mesenchymal cells of the portal tract stroma and vessels. In cirrhotic liver, PDGF-A and -B chain mRNA expression was markedly increased and was co-distributed with immunoreactivity for PDGF-AA and -BB in infiltrating inflammatory cells and along vascular structures within fibrous septa. These aspects were paralleled by a marked overexpression of PDGF-R alpha- and beta-subunit mRNAs and of the relative immunoreactivities in a wide range of mesenchymal cells in fibrous septa and in perisinusoidal alpha-smooth-muscle-actin-positive cells. In general expression and distribution of PDGF-R subunits appeared to be related to the activation of different mesenchymal cell types involved in the fibroproliferative process. Therefore, we evaluated the expression of PDGF-R subunits in liver tissue specimens with increasing degrees of necroinflammatory activity. The results of this additional study confirmed that expression of PDGF-R subunits is highly correlated with the severity of histological lesions and collagen deposition. Our results, providing evidence for a functional involvement of PDGF/PDGF-R in liver fibrogenesis, greatly support the results of previous in vitro studies and direct attention toward pharmacological strategies able to affect the series of signaling events arising from the autophosphorylation of PDGF-R subunits.
This article has been cited by other articles:
 |
|
 |
|
  J. Andrae, R. Gallini, and C. Betsholtz Role of platelet-derived growth factors in physiology and medicine Genes & Dev., May 15, 2008; 22(10): 1276 - 1312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Fu, S. Zheng, J. Lin, J. Ryerse, and A. Chen Curcumin Protects the Rat Liver from CCl4-Caused Injury and Fibrogenesis by Attenuating Oxidative Stress and Suppressing Inflammation Mol. Pharmacol., February 1, 2008; 73(2): 399 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Stock, D. Monga, X. Tan, A. Micsenyi, N. Loizos, and S. P.S. Monga Platelet-derived growth factor receptor-{alpha}: a novel therapeutic target in human hepatocellular cancer Mol. Cancer Ther., July 1, 2007; 6(7): 1932 - 1941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yang, C.-C. Chan, O.-S. Kwon, S. Liu, J. McGhee, S. A. Stimpson, L. Z. Chen, W. W. Harrington, W. T. Symonds, and D. C. Rockey Regulation of peroxisome proliferator-activated receptor-{gamma} in liver fibrosis Am J Physiol Gastrointest Liver Physiol, November 1, 2006; 291(5): G902 - G911. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E Novo, F Marra, E Zamara, L Valfre di Bonzo, L Monitillo, S Cannito, I Petrai, A Mazzocca, A Bonacchi, R S M De Franco, et al. Overexpression of Bcl-2 by activated human hepatic stellate cells: resistance to apoptosis as a mechanism of progressive hepatic fibrogenesis in humans Gut, August 1, 2006; 55(8): 1174 - 1182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mazzocca, S. C. Sciammetta, V. Carloni, L. Cosmi, F. Annunziato, T. Harada, S. Abrignani, and M. Pinzani Binding of Hepatitis C Virus Envelope Protein E2 to CD81 Up-regulates Matrix Metalloproteinase-2 in Human Hepatic Stellate Cells J. Biol. Chem., March 25, 2005; 280(12): 11329 - 11339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Abdollahi, M. Li, G. Ping, C. Plathow, S. Domhan, F. Kiessling, L. B. Lee, G. McMahon, H.-J. Grone, K. E. Lipson, et al. Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis J. Exp. Med., March 21, 2005; 201(6): 925 - 935. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Oleggini, L. Musante, S. Menoni, G. Botti, M. D. Duca, M. Prudenziati, A. Carrea, R. Ravazzolo, and G. M. Ghiggeri Characterization of a DNA binding site that mediates the stimulatory effect of cyclosporin-A on type III collagen expression in renal cells Nephrol. Dial. Transplant., June 1, 2000; 15(6): 778 - 785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-H. Heldin and B. Westermark Mechanism of Action and In Vivo Role of Platelet-Derived Growth Factor Physiol Rev, October 1, 1999; 79(4): 1283 - 1316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M V Apte, P S Haber, S J Darby, S C Rodgers, G W McCaughan, M A Korsten, R C Pirola, and J S Wilson Pancreatic stellate cells are activated by proinflammatory cytokines: implications for pancreatic fibrogenesis Gut, April 1, 1999; 44(4): 534 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mallat, C. Gallois, J. Tao, A. Habib, J. Maclouf, P. Mavier, A.-M. Preaux, and S. Lotersztajn Platelet-derived Growth Factor-BB and Thrombin Generate Positive and Negative Signals for Human Hepatic Stellate Cell Proliferation. ROLE OF A PROSTAGLANDIN/CYCLIC AMP PATHWAY AND CROSS-TALK WITH ENDOTHELIN RECEPTORS J. Biol. Chem., October 16, 1998; 273(42): 27300 - 27305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Robino, M. Parola, F. Marra, A. Caligiuri, R. M. S. De Franco, E. Zamara, G. Bellomo, P. Gentilini, M. Pinzani, and M. U. Dianzani Interaction between 4-Hydroxy-2,3-alkenals and the Platelet-derived Growth Factor-beta Receptor. REDUCED TYROSINE PHOSPHORYLATION AND DOWNSTREAM SIGNALING IN HEPATIC STELLATE CELLS J. Biol. Chem., December 15, 2000; 275(51): 40561 - 40567. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
