help button home button Am J Pathol ASIP 2008 Summer Academy, Molecular Methcanisms of Human Disease: Injury, Inflammation, and Tissue Repair
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 Aitken, K. J.
Right arrow Articles by Bägli, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Aitken, K. J.
Right arrow Articles by Bägli, D. J.
(American Journal of Pathology. 2006;169:459-470.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.050969

Mechanotransduction of Extracellular Signal-Regulated Kinases 1 and 2 Mitogen-Activated Protein Kinase Activity in Smooth Muscle Is Dependent on the Extracellular Matrix and Regulated by Matrix Metalloproteinases

Karen J. Aitken, Gregory Block, Armando Lorenzo, Daniel Herz, Nesrin Sabha, Omar Dessouki, France Fung, Marta Szybowska, Laura Craig and Darius J. Bägli

From the Research Institute and Division of Urology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

Excessive wall stretch of distensible hollow organs in cardiovascular and urinary systems can activate matrix metalloproteinases (MMPs), thereby releasing matrix neoepitopes and growth factor ligands, leading to ERK1/2 activation. However, the role of MMPs in mechanotransduction of ERK1/2 signaling in the bladder is unknown. We examined bladders undergoing sustained distension over time, which provides a novel platform for smooth muscle mechanotransduction studies. Bladder distension ex vivo caused increased proliferation and MMP activity. Conditioned medium from distended compared with undistended bladders induced proliferation in bladder smooth muscle cells (BSMCs). When conditioned medium from distended bladders was used to proteolyze collagen type I matrices, matrices augmented BSMC proliferation, which was inhibited if bladders were distended in presence of broad-spectrum MMP inhibitors. Distension of ex vivo bladders also induced ERK1/2 phosphorylation in situ, which was dependent on MMP activity in the intact bladder. Similarly, stretching BSMCs in vitro induced increases in ERK1/2 activation and ERK1/2-dependent proliferation under discrete mechanical conditions, and distension conditioned medium itself induced MMP-dependent ERK1/2 activation in BSMCs. Overall, stretch-induced proliferation and ERK1/2 signaling in bladder tissue and BSMCs likely depend on secreted MMP activity. Identification of intermediaries between MMPs and ERK1/2 may elaborate novel mechanisms underlying mechanotransduction in bladder smooth muscle.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Renal Physiol.Home page
M. Imamura, A. Kanematsu, S. Yamamoto, Y. Kimura, I. Kanatani, N. Ito, Y. Tabata, and O. Ogawa
Basic fibroblast growth factor modulates proliferation and collagen expression in urinary bladder smooth muscle cells
Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1007 - F1017.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the American Society for Investigative Pathology.