 |
||||
| 2007 JASN IMPACT FACTOR 7.111 | HOME AUTHOR INFO EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP | |||
| CURRENT ISSUE | ARCHIVES | JASN Express | ONLINE SUBMISSION | |
|
||||
| 2007 JASN IMPACT FACTOR 7.111 | HOME AUTHOR INFO EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP | |||
| CURRENT ISSUE | ARCHIVES | JASN Express | ONLINE SUBMISSION | |
*University of Washington and Children’s Hospital and Regional Medical Center, Division of Nephrology, Seattle, Washington; Department of Pathology, University of Washington, Seattle, Washington; 
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania; and The Center For Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium.
Correspondance to Dr. Allison A. Eddy, Children’s Hospital and Regional Medical Center, Division of Nephrology, Mail Stop 5G-1, 4800 Sand Point Way NE, Seattle, WA 98105. Phone: 206-987-2524; Fax: 206-987-2636;
ABSTRACT. The urokinase cellular receptor (uPAR) recognizes the N-terminal growth factor domain of urokinase-type plasminogen activator (uPA) and is expressed by several cell types. The present study was designed to test the hypothesis that uPAR regulates the renal fibrogenic response to chronic injury. Groups of uPAR wild-type (+/+) and deficient (-/-) mice were investigated between 3 and 14 d after unilateral ureteral obstruction (UUO) or sham surgery. Not detected in normal kidneys, uPAR mRNA was expressed in response to UUO in the +/+ mice. By in situ hybridization, uPAR mRNA transcripts were detected in renal tubules and interstitial cells of the obstructed uPAR+/+ kidneys. The severity of renal fibrosis, based on the measurement of total collagen (13.5 ± 1.5 versus 9.8 ± 1.0 µg/mg kidney on day 14; -/- versus +/+) and interstitial area stained by Masson trichrome (22 ± 4% versus 14 ± 3% on day 14; -/- versus +/+) was significantly greater in the uPAR-/- mice. In the absence of uPAR, renal uPA activity was significantly decreased compared with the wild-type animals after UUO (62 ± 20 versus 135 ± 13 units at day 3 UUO; 74 ± 17 versus 141 ± 16 at day 7 UUO; 98 ± 20 versus 165 ± 10 at day 14 UUO; -/- versus +/+). In contrast, renal expression of several genes that regulate plasmin activity were similar in both genotypes, including uPA, tPA, PAI-1, protease nexin-1, and 
2-antiplasmin. Worse renal fibrosis in the uPAR-/- mice appears to be TGF-
-independent, as TGF- activity was actually reduced by 65% in the -/- mice despite similar renal TGF-1 mRNA levels. Significantly lower levels of the major 2.3-kb transcript and the 69-kd active protein of hepatocyte growth factor (HGF), a known anti-fibrotic growth factor, in the uPAR-/- mice suggests a potential link between HGF and the renoprotective effects of uPAR. These data suggest that renal uPAR attenuates the fibrogenic response to renal injury, an outcome that is mediated in part by urokinase-dependent but plasminogen-independent functions. E-mail: allison.eddy@seattlechildrens.org
This article has been cited by other articles:
 |
|
 |
|
  S. D'Alessio, L. Gerasi, and F. Blasi uPAR-deficient mouse keratinocytes fail to produce EGFR-dependent laminin-5, affecting migration in vivo and in vitro J. Cell Sci., December 1, 2008; 121(23): 3922 - 3932. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Horowitz, D. S. Rogers, R. H. Simon, T. H. Sisson, and V. J. Thannickal Plasminogen Activation Induced Pericellular Fibronectin Proteolysis Promotes Fibroblast Apoptosis Am. J. Respir. Cell Mol. Biol., January 1, 2008; 38(1): 78 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Leduc, N. Beaufort, S. de Bentzmann, J.-C. Rousselle, A. Namane, M. Chignard, and D. Pidard The Pseudomonas aeruginosa LasB Metalloproteinase Regulates the Human Urokinase-Type Plasminogen Activator Receptor through Domain-Specific Endoproteolysis Infect. Immun., August 1, 2007; 75(8): 3848 - 3858. [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]
|
|
|
|
|
|
D. Cosgrove A complex, tissue-specific role for plasmin and its regulators in modulating fibrogenic activity Am J Physiol Renal Physiol, July 1, 2007; 293(1): F10 - F11. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Zhang, K. A. Kernan, S. J. Collins, X. Cai, J. M. Lopez-Guisa, J. L. Degen, Y. Shvil, and A. A. Eddy Plasmin(ogen) Promotes Renal Interstitial Fibrosis by Promoting Epithelial-to-Mesenchymal Transition: Role of Plasmin-Activated Signals J. Am. Soc. Nephrol., March 1, 2007; 18(3): 846 - 859. [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]
|
|
|
|
 |
|
 K. Hu, J. Yang, S. Tanaka, S. L. Gonias, W. M. Mars, and Y. Liu Tissue-type Plasminogen Activator Acts as a Cytokine That Triggers Intracellular Signal Transduction and Induces Matrix Metalloproteinase-9 Gene Expression J. Biol. Chem., January 27, 2006; 281(4): 2120 - 2127. [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]
|
|
|
|
|
|
J. J.T.H. Roelofs, K. M.A. Rouschop, J. C. Leemans, N. Claessen, A. M. de Boer, W. M. Frederiks, H.R. Lijnen, J. J. Weening, and S. Florquin Tissue-Type Plasminogen Activator Modulates Inflammatory Responses and Renal Function in Ischemia Reperfusion Injury J. Am. Soc. Nephrol., January 1, 2006; 17(1): 131 - 140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Koh, S. C. Bryer, A. M. Pucci, and T. H. Sisson Mice deficient in plasminogen activator inhibitor-1 have improved skeletal muscle regeneration Am J Physiol Cell Physiol, July 1, 2005; 289(1): C217 - C223. [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]
|
|
|
|
|
|
G. Zhang, X. Cai, J. M. Lopez-Guisa, S. J. Collins, and A. A. Eddy Mitogenic Signaling of Urokinase Receptor-Deficient Kidney Fibroblasts: Actions of an Alternative Urokinase Receptor and LDL Receptor-Related Protein J. Am. Soc. Nephrol., August 1, 2004; 15(8): 2090 - 2102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhou, J. S. Hagood, and J. E. Murphy-Ullrich Thy-1 Expression Regulates the Ability of Rat Lung Fibroblasts to Activate Transforming Growth Factor-{beta} in Response to Fibrogenic Stimuli Am. J. Pathol., August 1, 2004; 165(2): 659 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liu Hepatocyte growth factor in kidney fibrosis: therapeutic potential and mechanisms of action Am J Physiol Renal Physiol, July 1, 2004; 287(1): F7 - F16. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Sunami, H. Sugiyama, D.-H. Wang, M. Kobayashi, Y. Maeshima, Y. Yamasaki, N. Masuoka, N. Ogawa, S. Kira, and H. Makino Acatalasemia sensitizes renal tubular epithelial cells to apoptosis and exacerbates renal fibrosis after unilateral ureteral obstruction Am J Physiol Renal Physiol, June 1, 2004; 286(6): F1030 - F1038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Eddy Proteinuria and interstitial injury Nephrol. Dial. Transplant., February 1, 2004; 19(2): 277 - 281. [Full Text] [PDF]
|
|
|
|
|
|
V. Eis, B. Luckow, V. Vielhauer, J. T. Siveke, Y. Linde, S. Segerer, G. P. de Lema, C. D. Cohen, M. Kretzler, M. Mack, et al. Chemokine Receptor CCR1 But Not CCR5 Mediates Leukocyte Recruitment and Subsequent Renal Fibrosis after Unilateral Ureteral Obstruction J. Am. Soc. Nephrol., February 1, 2004; 15(2): 337 - 347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zhang, H. Kim, X. Cai, J. M. Lopez-Guisa, P. Carmeliet, and A. A. Eddy Urokinase Receptor Modulates Cellular and Angiogenic Responses in Obstructive Nephropathy J. Am. Soc. Nephrol., May 1, 2003; 14(5): 1234 - 1253. [Abstract] [Full Text] [PDF]
|
|
|
HOME
CURRENT ISSUE
ARCHIVES
JASN Express
ONLINE SUBMISSION
AUTHOR INFO
EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP |
Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673
