| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Invited Review
Division of Cellular and Molecular Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261
Hepatocyte growth factor (HGF) is a pleiotropic factor that plays an imperative role in tubular repair and regeneration after acute renal injury. Growing evidence indicates that HGF is also an endogenous renoprotective factor that possesses a potent antifibrotic ability. HGF prevents the initiation and progression of chronic renal fibrosis and inhibits transforming growth factor (TGF)-
1 expression in a wide variety of animal models. In vitro, HGF counteracts the action of TGF-1 in different types of kidney cells, resulting in blockade of the myofibroblastic activation from interstitial fibroblasts and glomerular mesangial cells, as well as inhibition of the mesenchymal transition from tubular epithelial cells. Recent studies reveal that HGF antagonizes the profibrotic actions of TGF-1 by intercepting Smad signal transduction through diverse mechanisms. In interstitial fibroblasts, HGF blocks activated Smad-2/3 nuclear translocation, whereas it specifically upregulates the expression of the Smad transcriptional corepressor SnoN in tubular epithelial cells. In glomerular mesangial cells, HGF stabilizes another Smad corepressor, TGIF, by preventing it from degradation. Smad corepressors bind to activated Smad-2/3 and sequester their ability to transcriptionally activate TGF- target genes. This article reviews recent advances in our understanding of the cellular and molecular mechanisms underlying HGF inhibition of renal fibrosis.
c-met; transforming growth factor-1; Smad; myofibroblasts
This article has been cited by other articles:
|
|
 |
|
  X. Tan, X. Wen, and Y. Liu Paricalcitol Inhibits Renal Inflammation by Promoting Vitamin D Receptor-Mediated Sequestration of NF-{kappa}B Signaling J. Am. Soc. Nephrol., September 1, 2008; 19(9): 1741 - 1752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Aydin, S. Signorelli, T. Lechleitner, M. Joannidis, C. Pleban, P. Perco, W. Pfaller, and P. Jennings Influence of microvascular endothelial cells on transcriptional regulation of proximal tubular epithelial cells Am J Physiol Cell Physiol, February 1, 2008; 294(2): C543 - C554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Boor, K. Sebekova, T. Ostendorf, and J. Floege Treatment targets in renal fibrosis Nephrol. Dial. Transplant., December 1, 2007; 22(12): 3391 - 3407. [Full Text] [PDF]
|
|
|
|
|
|
H. Guo, J. C.K. Leung, M. F. Lam, L. Y.Y. Chan, A. W.L. Tsang, H. Y. Lan, and K. N. Lai Smad7 Transgene Attenuates Peritoneal Fibrosis in Uremic Rats Treated with Peritoneal Dialysis J. Am. Soc. Nephrol., October 1, 2007; 18(10): 2689 - 2703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Haydont, C. Bourgier, M. Pocard, A. Lusinchi, J. Aigueperse, D. Mathe, J. Bourhis, and M.-C. Vozenin-Brotons Pravastatin Inhibits the Rho/CCN2/Extracellular Matrix Cascade in Human Fibrosis Explants and Improves Radiation-Induced Intestinal Fibrosis in Rats Clin. Cancer Res., September 15, 2007; 13(18): 5331 - 5340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Tan, X. Zhang, J. Yang, Y. Li, and Y. Liu Molecular Basis for the Cell Type Specific Induction of SnoN Expression by Hepatocyte Growth Factor J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2340 - 2349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Yamaguchi, J. M. Lopez-Guisa, X. Cai, S. J. Collins, D. M. Okamura, and A. A. Eddy Endogenous urokinase lacks antifibrotic activity during progressive renal injury Am J Physiol Renal Physiol, July 1, 2007; 293(1): F12 - F19. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yoshikawa, K. Hishikawa, T. Marumo, and T. Fujita Inhibition of Histone Deacetylase Activity Suppresses Epithelial-to-Mesenchymal Transition Induced by TGF-beta1 in Human Renal Epithelial Cells J. Am. Soc. Nephrol., January 1, 2007; 18(1): 58 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zhang, Z. Dong, and T. Yang Prostaglandin D2 inhibits TGF-beta1-induced epithelial-to-mesenchymal transition in MDCK cells Am J Physiol Renal Physiol, December 1, 2006; 291(6): F1332 - F1342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Eddy and A. B. Fogo Plasminogen Activator Inhibitor-1 in Chronic Kidney Disease: Evidence and Mechanisms of Action J. Am. Soc. Nephrol., November 1, 2006; 17(11): 2999 - 3012. [Full Text] [PDF]
|
|
|
|
|
|
G. Athauda, A. Giubellino, J. A. Coleman, C. Horak, P. S. Steeg, M.-J. Lee, J. Trepel, J. Wimberly, J. Sun, A. Coxon, et al. c-Met Ectodomain Shedding Rate Correlates with Malignant Potential. Clin. Cancer Res., July 15, 2006; 12(14): 4154 - 4162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-L. Xia, C. Dai, G. K. Michalopoulos, and Y. Liu Hepatocyte Growth Factor Attenuates Liver Fibrosis Induced by Bile Duct Ligation Am. J. Pathol., May 1, 2006; 168(5): 1500 - 1512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Giannopoulou, S. C. Iszkula, C. Dai, X. Tan, J. Yang, G. K. Michalopoulos, and Y. Liu Distinctive role of Stat3 and Erk-1/2 activation in mediating interferon-{gamma} inhibition of TGF-beta1 action Am J Physiol Renal Physiol, May 1, 2006; 290(5): F1234 - F1240. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, X. Wen, B. C. Spataro, K. Hu, C. Dai, and Y. Liu Hepatocyte Growth Factor Is a Downstream Effector that Mediates the Antifibrotic Action of Peroxisome Proliferator-Activated Receptor-{gamma} Agonists J. Am. Soc. Nephrol., January 1, 2006; 17(1): 54 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Bottaro and W. M. Linehan Multifocal Renal Cancer: Genetic Basis and Its Medical Relevance Clin. Cancer Res., October 15, 2005; 11(20): 7206 - 7208. [Full Text] [PDF]
|
|
|
|
|
|
C. Chatziantoniou and J.-C. Dussaule Insights into the mechanisms of renal fibrosis: is it possible to achieve regression? Am J Physiol Renal Physiol, August 1, 2005; 289(2): F227 - F234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Hirschberg Wound Healing in the Kidney: Complex Interactions in Renal Interstitial Fibrogenesis J. Am. Soc. Nephrol., January 1, 2005; 16(1): 9 - 11. [Full Text] [PDF]
|
|
|
|
|
|
J. Yang, C. Dai, and Y. Liu A Novel Mechanism by which Hepatocyte Growth Factor Blocks Tubular Epithelial to Mesenchymal Transition J. Am. Soc. Nephrol., January 1, 2005; 16(1): 68 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhang, J. Yang, Y. Li, and Y. Liu Both Sp1 and Smad participate in mediating TGF-{beta}1-induced HGF receptor expression in renal epithelial cells Am J Physiol Renal Physiol, January 1, 2005; 288(1): F16 - F26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gong, A. Rifai, E. M. Tolbert, P. Biswas, J. N. Centracchio, and L. D. Dworkin Hepatocyte Growth Factor Ameliorates Renal Interstitial Inflammation in Rat Remnant Kidney by Modulating Tubular Expression of Macrophage Chemoattractant Protein-1 and RANTES J. Am. Soc. Nephrol., November 1, 2004; 15(11): 2868 - 2881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Dai, J. Yang, S. Bastacky, J. Xia, Y. Li, and Y. Liu Intravenous Administration of Hepatocyte Growth Factor Gene Ameliorates Diabetic Nephropathy in Mice J. Am. Soc. Nephrol., October 1, 2004; 15(10): 2637 - 2647. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
