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About the Authors:
Preston E. Bratcher
* E-mail: [email protected]
Affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
Nathaniel M. Weathington
Affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America
Heidi J. Nick
Affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
Patricia L. Jackson
Affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
Robert J. Snelgrove
Affiliation: National Heart and Lung Institute, Imperial College London, London, United Kingdom
Amit Gaggar
Affiliations Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, University of Alabama at Birmingham Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, Medicine Service, United States Department of Veterans Affairs Medical Center, Birmingham, Alabama, United States of America
Introduction
Of the more than twenty matrix metalloproteases, matrix metalloprotease 9 (MMP-9) is one of the most well studied, both in vitro and in vivo, within the context of normal and several disease states. Also known as 92-kDa gelatinase, or gelatinase B, MMP-9 has a variety of substrates and roles in functions as diverse as tissue remodeling, tissue repair, and regulation of inflammation [1]. More than 30 substrates have been discovered for MMP-9, including gelatin, type IV and V collagens, TNF-α, a variety of surface receptors [including vascular endothelial growth factor receptor-2, beta2-adrenergic receptor, and ICAM-1 (reviewed in [2]], protease nexin-1, interleukin (IL) 8, IL-1β, and leukemia inhibitory factor [3], [4], [5], [6], [7]. MMP-9 has a structure similar to other matrix metalloproteases, and includes four domains: an N-terminal signal sequence, a pro-domain region, an active catalytic domain, and a hemopexin-like C-terminal domain (reviewed in [8]). The prodomain region must be cleaved in order for the protein to become active.
Due to its many functions in the body, MMP-9 dysregulation has been implicated in a variety of diseases. MMP-9 expression and activation levels have been shown to be elevated in lower airway secretions and/or serum of smokers and patients with chronic obstructive pulmonary...