Biology Reference
In-Depth Information
Chapter 1
Matrix Metalloproteinases and Their Inhibitors
in Turnover and Degradation of Extracellular
Matrix
Sean E. Gill and William C. Parks
Abstract As their names imply, matrix metalloproteinases (MMPs) are thought to
degrade or turnover extracellular matrix (ECM) proteins. Although some MMPs
have prominent roles in ECM metabolism, most members of this large gene family,
however, have either limited or no demonstrated roles in ECM turnover. In vivo
studies of MMP function have revealed that matrix degradation per se is neither the
sole nor predominant function of these proteinases and that these proteinases act on
a variety of extracellular protein substrates, often to mediate gain-of-function
processing. Because their substrates are diverse, MMPs have emerged as critical
effectors in a variety of homeostatic functions, such as bone remodeling, wound
healing, metabolism, and several aspects of immunity and inflammation. However,
MMPs are also involved in a number of pathological processes, such as tumor
progression, fibrosis, chronic inflammation, and vascular disease. In this chapter,
we discuss the role of MMPs in affecting ECMmetabolism and aspects of how their
catalytic activity is regulated, with an emphasis on the action of the tissue inhibitors
of metalloproteinases (TIMPs).
1.1 Matrix Metalloproteinases
1.1.1
Introduction
Like serine and cysteine proteinases, the other families of proteinases discussed
in this volume, metalloproteases comprise a large family of endopeptidases. All
metalloproteinases contain an active site Zn
2+
(hence the prefix “metallo”), and the
nearly 200 members found in mammals (Puente et al.
2003
) are divided into
subfamilies or clans based on evolutionary relationships and structure of the
S.E. Gill (
*
) and W.C. Parks
Center for Lung Biology, University of Washington, 815 Mercer Street, Seattle, WA 98109, USA
e-mail: segill@uw.edu
