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  • Review Article
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The bladder extracellular matrix. Part I: architecture, development and disease

Nature Reviews Urology volume 6, pages 596–611 (2009)Cite this article

Abstract

From the earliest studies with epithelial cells implanted into detrusor muscle to later experiments on smooth muscle in defined collagen gels, cell niche and extracellular matrix (ECM) have been clearly shown to orchestrate cellular behavior and fate whether quiescent, migratory, or proliferative. Normal matrix can revert transformed cells to quiescence, and damaged matrix can trigger malignancy or dedifferentiation. ECM influence in disease, development, healing and regeneration has been demonstrated in many other fields of study, but a thorough examination of the roles of ECM in bladder cell activity has not yet been undertaken. Structural ECM proteins, in concert with adhesive proteins, provide crucial structural support to the bladder. Both structural and nonstructural components of the bladder have major effects on smooth muscle function, through effects on matrix rigidity and signaling through ECM receptors. While many ECM components and receptors identified in the bladder have specific known functions in the vascular smooth musculature, their function in the bladder is often less well defined. In cancer and obstructive disease, the ECM has a critical role in pathogenesis. The challenge in these settings will be to find therapies that prevent hyperproliferation and encourage proper differentiation, through an understanding of matrix effects on cell biology and susceptibility to therapeutics.

Key Points

  • The bladder extracellular matrix (ECM) is in a dynamic conversation with its constituent cells through a variety of ECM receptors, which have crucial roles in proliferation, differentiation and homeostatic cell responses

  • The bladder ECM responds to strain injury or obstruction by increasing levels of matrix metalloproteinases, tissue inhibitors of metalloproteinases, collagen III, and many smaller components of the matrix

  • Alterations in ECM proteins can lead to changes in the stiffness of the matrix, which is a critical mediator of intracellular tension and cell behavior

  • Damaged matrix that results from bladder overdistention can cause long-lasting changes in smooth muscle cell behavior

  • Ascribing matrix changes to simple upregulation or downregulation of ECM gene expression neglects ECM alterations due to cross-linkages, proteolysis or glycosylation, which have a profound effect on distension and strength of the bladder wall

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Figure 1: Dynamic reciprocity.
Figure 2: The proposed MMP7–CD44–HB-EGF complex in bladder smooth muscle cell mitogenicity.
Figure 3: Effects of damaged ECM on smooth muscle cell phenotype.

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  1. Divisions of Developmental & Stem Cell Biology, and Urology, The Hospital For Sick Children, University of Toronto, ON, Canada

    Karen J. Aitken & Darius J. Bägli

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Supplementary Figure 1

Hyaluronic acid rapidly responds to strain in the detrusor muscle region. (PPT 1896 kb)

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Aitken, K., Bägli, D. The bladder extracellular matrix. Part I: architecture, development and disease. Nat Rev Urol 6, 596–611 (2009). https://doi.org/10.1038/nrurol.2009.201

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