| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 142, 59-70, Copyright © 1993 by American Society for Investigative Pathology
REGULAR ARTICLES |
M Keeton, Y Eguchi, M Sawdey, C Ahn and DJ Loskutoff
Committee on Vascular Biology, Scripps Research Institute, La Jolla, CA 92037.
Type 1 plasminogen activator inhibitor (PAI-1) may be markedly increased in the plasma of patients with endotoxemia and/or renal disease. To investigate renal PAI-1 production during acute endotoxemia, a murine model system was used. Mice were injected with either saline alone or saline containing 50 micrograms endotoxin, and sacrificed 3 hours later and their tissues analyzed for PAI-1 messenger RNA (mRNA) and antigen. Northern blot analysis confirmed that the level of renal PAI-1 mRNA was greatly increased in the endotoxemic mice relative to the saline controls. In situ hybridization was then performed to determine the cellular localization of PAI-1 mRNA within the renal tissues. In the control kidneys, low levels of PAI-1 mRNA were detected in the renal papilla and in the muscular walls of renal arteries. However, in the endotoxemic mice, an intense hybridization signal for PAI-1 mRNA was observed in glomerular and peritubular cells. These cells also stained positively for von Willebrand factor antigen, an endothelial cell-specific marker. The PAI-1 mRNA hybridization signal could further be observed in peritubular endothelial cells in the medulla and in endothelial cells of veins and arteries throughout the kidney. Immunochemical analysis revealed that PAI-1 antigen co- localized to the cytoplasm of cells expressing PAI-1 mRNA. This study provides the first direct evidence that PAI-1 is induced in endothelial cells of the kidney during endotoxemia in vivo and suggests a role for PAI-1 in the pathogenesis of renal disease.
This article has been cited by other articles:
 |
|
 |
|
  K. Schafer, K. Muller, A. Hecke, E. Mounier, J. Goebel, D. J. Loskutoff, and S. Konstantinides Enhanced Thrombosis in Atherosclerosis-Prone Mice Is Associated With Increased Arterial Expression of Plasminogen Activator Inhibitor-1 Arterioscler. Thromb. Vasc. Biol., November 1, 2003; 23(11): 2097 - 2103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Pawlinski, B. Pedersen, B. Kehrle, W. C. Aird, R. D. Frank, M. Guha, and N. Mackman Regulation of tissue factor and inflammatory mediators by Egr-1 in a mouse endotoxemia model Blood, May 15, 2003; 101(10): 3940 - 3947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yamamoto, T. Shimokawa, H. Yi, K.-i. Isobe, T. Kojima, D. J. Loskutoff, and H. Saito Aging Accelerates Endotoxin-Induced Thrombosis : Increased Responses of Plasminogen Activator Inhibitor-1 and Lipopolysaccharide Signaling with Aging Am. J. Pathol., November 1, 2002; 161(5): 1805 - 1814. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Eddy Plasminogen activator inhibitor-1 and the kidney Am J Physiol Renal Physiol, August 1, 2002; 283(2): F209 - F220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Samad, M. Pandey, and D. J. Loskutoff Regulation of tissue factor gene expression in obesity Blood, December 1, 2001; 98(12): 3353 - 3358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Venugopal, R. Sharon, R. Abramovitz, A. Khasin, and R. Miskin Plasminogen activator inhibitor-1 in cardiovascular cells: rapid induction after injecting mice with kainate or adrenergic agents Cardiovasc Res, February 1, 2001; 49(2): 476 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kawasaki, M. Dewerchin, H. R. Lijnen, J. Vermylen, and M. F. Hoylaerts Vascular release of plasminogen activator inhibitor-1 impairs fibrinolysis during acute arterial thrombosis in mice Blood, July 1, 2000; 96(1): 153 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Samad, K. T. Uysal, S. M. Wiesbrock, M. Pandey, G. S. Hotamisligil, and D. J. Loskutoff Tumor necrosis factor alpha is a key component in the obesity-linked elevation of plasminogen activator inhibitor 1 PNAS, June 8, 1999; 96(12): 6902 - 6907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yamamoto, V. de Waard, C. Fearns, and D. J. Loskutoff Tissue Distribution and Regulation of Murine von Willebrand Factor Gene Expression In Vivo Blood, October 15, 1998; 92(8): 2791 - 2801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Coffman, R. F. Spurney, R. B. Mannon, and R. Levenson Thromboxane A2 modulates the fibrinolytic system in glomerular mesangial cells Am J Physiol Renal Physiol, August 1, 1998; 275(2): F262 - F269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yamamoto and D. J. Loskutoff Extrahepatic Expression and Regulation of Protein C in the Mouse Am. J. Pathol., August 1, 1998; 153(2): 547 - 555. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Samad, M. Pandey, and D. J. Loskutoff Tissue factor gene expression in the adipose tissues of obese mice PNAS, June 23, 1998; 95(13): 7591 - 7596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Dong, A. H. Schulick, M. B. DeYoung, and D. A. Dichek Identification of a cis-Acting Sequence in the Human Plasminogen Activator Inhibitor Type-1 Gene That Mediates Transforming Growth Factor-beta 1 Responsiveness in Endothelium in Vivo J. Biol. Chem., November 22, 1996; 271(47): 29969 - 29977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. H. Lundgren, S. L. Brown, T. K. Nordt, B. E. Sobel, and S. Fujii Elaboration of Type-1 Plasminogen Activator Inhibitor From Adipocytes : A Potential Pathogenetic Link Between Obesity and Cardiovascular Disease Circulation, January 1, 1996; 93(1): 106 - 110. [Abstract] [Full Text]
|
|
|
|
|
|
P.N. Raghunath, J. E. Tomaszewski, S. T. Brady, R. J. Caron, S. S. Okada, and E. S. Barnathan Plasminogen Activator System in Human Coronary Atherosclerosis Arterioscler. Thromb. Vasc. Biol., September 1, 1995; 15(9): 1432 - 1443. [Abstract] [Full Text]
|
|
|
|
|
|
J. T. Seykora, L. Mei, G. P. Dotto, and P. L. Stein `Srcasm: a Novel SrcActivating and Signaling Molecule J. Biol. Chem., January 18, 2002; 277(4): 2812 - 2822. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
