help button home button Am J Pathol R & D Systems
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by D’Andrea, M. R.
Right arrow Articles by Saban, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by D’Andrea, M. R.
Right arrow Articles by Saban, R.
(American Journal of Pathology. 2003;162:907-923.)
© 2003 American Society for Investigative Pathology

Expression of Protease-Activated Receptor-1, -2, -3, and -4 in Control and Experimentally Inflamed Mouse Bladder

Michael R. D’Andrea*, Marcia R. Saban{dagger}, Ngoc-Bich Nguyen{dagger}, Patricia Andrade-Gordon* and Ricardo Saban{dagger}

From Johnson and Johnson Pharmaceutical Research and Development,* Spring House, Pennsylvania; and the Department of Physiology,{dagger} The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma

Inflammation underlines all major bladder pathologies and represents a defense reaction to injury involving a mandatory participation of mast cells and sensory nerves. Mast cells are particularly frequent in close proximity to epithelial surfaces where they are strategically located in the bladder and release their mediators in response to inflammation. Tryptase is specifically produced by mast cells and modulates inflammation by activating protease-activated receptors (PARs). We recently found that PAR-4 mRNA is up-regulated in experimental bladder inflammation regardless of the initiating stimulus. Because it has been reported that PAR-1, PAR-2, and PAR-3 may also be involved in the processes of inflammation, we used immunohistochemistry to characterize the expression of all known PARs in normal, acute, and chronic inflamed mouse bladder. We found that all four PARs are present in the control mouse bladder, and follow a unique distribution. All four PARs are co-expressed in the urothelium, whereas PAR-1 and PAR-2 are predominant in the detrusor muscle, and PAR-4 is expressed in peripheral nerves and plexus cell bodies. The strong expression of PARs in the detrusor muscle indicates the need for studies on the role of these receptors in motility whereas the presence of PAR-4 in nerves may indicate its participation in neurogenic inflammation. In addition, PARs are differentially modulated during inflammation. PAR-1 and PAR-2 are down-regulated in acute inflammation whereas PAR-3 and PAR-4 are up-regulated. Bladder fibroblasts were found to present a clear demarcation in PAR expression secondary to acute and chronic inflammation. Our findings provide evidence of participation of PARs in the urinary system, provide a working model for mast cell tryptase signaling in the mouse bladder, and evoke testable hypotheses regarding the roles of PARs in bladder inflammation. It is timely to understand the role of tryptase signaling and PARs in the context of bladder biology.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Renal Physiol.Home page
M. R. Saban, J. M. Backer, M. V. Backer, J. Maier, B. Fowler, C. A. Davis, C. Simpson, X.-R. Wu, L. Birder, M. R. Freeman, et al.
VEGF receptors and neuropilins are expressed in the urothelial and neuronal cells in normal mouse urinary bladder and are upregulated in inflammation
Am J Physiol Renal Physiol, July 1, 2008; 295(1): F60 - F72.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
P. Rastogi, A. Rickard, N. Dorokhov, D. J. Klumpp, and J. McHowat
Loss of prostaglandin E2 release from immortalized urothelial cells obtained from interstitial cystitis patient bladders
Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1129 - F1135.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
A. Rullier, J. Gillibert-Duplantier, P. Costet, G. Cubel, V. Haurie, C. Petibois, D. Taras, N. Dugot-Senant, G. Deleris, P. Bioulac-Sage, et al.
Protease-activated receptor 1 knockout reduces experimentally induced liver fibrosis
Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G226 - G235.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. H. Slofstra, M. F. Bijlsma, A. P. Groot, P. H. Reitsma, T. Lindhout, H. ten Cate, and C. A. Spek
Protease-activated receptor-4 inhibition protects from multiorgan failure in a murine model of systemic inflammation
Blood, November 1, 2007; 110(9): 3176 - 3182.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. Ramachandran, L. R. Sadofsky, Y. Xiao, A. Botham, M. Cowen, A. H. Morice, and S. J Compton
Inflammatory mediators modulate thrombin and cathepsin-G signaling in human bronchial fibroblasts by inducing expression of proteinase-activated receptor-4
Am J Physiol Lung Cell Mol Physiol, March 1, 2007; 292(3): L788 - L798.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
L. A. Birder
More than just a barrier: urothelium as a drug target for urinary bladder pain
Am J Physiol Renal Physiol, September 1, 2005; 289(3): F489 - F495.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
M. R. D'Andrea, J. M. Mei, R. W. Tuman, R. A. Galemmo, and D. L. Johnson
Validation of in vivo pharmacodynamic activity of a novel PDGF receptor tyrosine kinase inhibitor using immunohistochemistry and quantitative image analysis
Mol. Cancer Ther., August 1, 2005; 4(8): 1198 - 1204.
[Abstract] [Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
M. R. D'Andrea, Y. Qiu, D. Haynes-Johnson, S. Bhattacharjee, P. Kraft, and S. Lundeen
Expression of PDE11A in Normal and Malignant Human Tissues
J. Histochem. Cytochem., July 1, 2005; 53(7): 895 - 903.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
E. S. Kimball, J. M. Palmer, M. R. D'Andrea, P. J. Hornby, and P. R. Wade
Acute colitis induction by oil of mustard results in later development of an IBS-like accelerated upper GI transit in mice
Am J Physiol Gastrointest Liver Physiol, June 1, 2005; 288(6): G1266 - G1273.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
R. M. Adam, S. H. Eaton, C. Estrada, A. Nimgaonkar, S.-C. Shih, L. E. H. Smith, I. S. Kohane, D. Bagli, and M. R. Freeman
Mechanical stretch is a highly selective regulator of gene expression in human bladder smooth muscle cells
Physiol Genomics, December 15, 2004; 20(1): 36 - 44.
[Abstract] [Full Text] [PDF]

Home page
 NeuroscientistHome page
T. Rohatgi, F. Sedehizade, K. G. Reymann, and G. Reiser
Protease-Activated Receptors in Neuronal Development, Neurodegeneration, and Neuroprotection: Thrombin as Signaling Molecule in the Brain
Neuroscientist, December 1, 2004; 10(6): 501 - 512.
[Abstract] [PDF]

Home page
 GutHome page
F Mule, R Pizzuti, A Capparelli, and N Vergnolle
Evidence for the presence of functional protease activated receptor 4 (PAR4) in the rat colon
Gut, February 1, 2004; 53(2): 229 - 234.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
I. Dozmorov, M. R. Saban, N. Knowlton, M. Centola, and R. Saban
Connective molecular pathways of experimental bladder inflammation
Physiol Genomics, November 11, 2003; 15(3): 209 - 222.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2003 by the American Society for Investigative Pathology.