MMPs and matrix proteases are critical effectors of cell responses. This function is ever more pertinent to dynamic states in which cells have to interact with their surrounding matrix to perform physiologic functions, or in disease states. Blood vessels undergo dynamic changes of their component cells to adapt to stresses or maladapt and cause disease. MMPs are intimately involved in these processes, but as apparent with the data presented herein, manipulation of MMP activity to modify the course of diseases may lead to adverse and unforeseen consequences.


Metalloproteases: Protein molecules (enzymes) that require the presence of metal ion bound to their sequence to maintain a proper structure that allows their functional activity. The main function of metalloproteases is to activate or to inactivate (inhibit) other proteins (substrates), usually by cutting off one or more of their fragments.

Multidomain structure: Domains are regions in a protein molecule that are determined by amino-acid sequence and that form defined, functionally distinct units. Thus, multidomain structure is specific for and characterizes a particular protein. If several proteins have similar multidomain structure, it means these proteins may also have similar functions.


1. Stocker, W., Grams, F., Baumann, U., Reinemer, P., Gomis-Ruth, F. X., McKay, D. B., and Bode, W. (1995). The metzincins—topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a superfamily of zinc-peptidases. Protein Sci. 4, 823-840.

2. Visse, R., and Nagase, H. (2003). Matrix metalloproteinases and tissue inhibitors of metalloproteinases: Structure, function, and biochemistry. Circ. Res. 92, 827-839. An updated review of biochemical structure of metaloproteinases and their specific inhibitors.

3. Andreini, C., Banci, L., Bertini, I., Luchinat, C., and Rosato, A. (2004). Bioinformatic comparison of structures and homology-models of matrix metalloproteinases. J. Proteome. Res. 3, 21-31.

4. Sternlicht, M. D., and Werb, Z. (2001). How matrix metalloproteinases regulate cell behavior. Ann. Rev. Cell Develop. Biol. 17, 463-516. An overview of the role of metaloproteinases in physiological processes that involve tissue remodeling.

5. Morgunova, E., Tuuttila, A., Bergmann, U., Isupov, M., Lindqvist, Y., Schneider, G., and Tryggvason, K. (1999). Structure of human promatrix metalloproteinase-2: Activation mechanism revealed. Science 284, 1667-1670.

6. Lambert, E., Dasse, E., Haye, B., and Petitfrere, E. (2004). TIMPs as multifacial proteins. Crit. Rev. Oncol./Hematol. 49, 187-198.

7. Hall, M. C., Young, D. A., Waters, J. G., Rowan, A. D., Chantry, A., Edwards, D. R., and Clark, I. M. (2003). The comparative role of activator protein 1 and Smad factors in the regulation of Timp-1 and MMP-1 gene expression by transforming growth factor-beta 1. J. Bio. Chem. 278, 10304-10313. An excellent example of modern, basic research on how tissue growth factor beta regulates expression of met-aloproteinase and specific metaloproteinase inhibitor genes to control cell behavior.

8. Yuan, W., and Varga, J. (2001). Transforming growth factor-beta repression of matrix metalloproteinase-1 in dermal fibroblasts involves Smad3. J. Bio. Chem. 276, 38502-38510.

9. Stamenkovic, I. (2003). Extracellular matrix remodelling: The role of matrix metalloproteinases. J. Pathol. 200, 448-464.

10. Heissig, B., Hattori, K., Dias, S., Friedrich, M., Ferris, B., Hackett, N. R., Crystal, R. G., Besmer, P., Lyden, D., Moore, M. A. S., Werb, Z., and Rafii, S. (2002). Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of Kit-ligand. Cell 109, 625-637.

11. Bellon, G., Martiny, L., and Robinet, A. (2004). Matrix metallopro-teinases and matrikines in angiogenesis. Crit. Rev. Oncol./Hematol. 49, 203-220.

12. Rabinovitch, M. (1999). EVE and beyond, retro and prospective insights. Am. J. Physiol. 277, L5-L12.

13. Novotna, H. J. (2002). Possible role of matrix metalloproteinases in reconstruction of peripheral pulmonary arteries induced by hypoxia. Physiol. Res. 51, 323-334.

His interests are focused on pulmonary pathology and molecular mechanisms responsible for pulmonary diseases. His grants are supported by the NIH/NHLBI, AHA, and other foundations.

Dr. Iwona Fijalkowska is a Research Associate in Cardiopulmonary Pathology in the Department of Pathology, Johns Hopkins University School of Medicine. Her scientific interests cover protein chemistry and protein-protein interactions in angiogenesis and hemostasis.

Capsule Biographies

Dr. Rubin M. Tuder, Professor of Pathology and Medicine, in the Department of Pathology, Johns Hopkins University School of Medicine.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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