Diverse functions of matrix metalloproteinases during fibrosis.
Fibrosis--a debilitating condition that can occur in most organs - is characterized by excess deposition of a collagen-rich extracellular matrix (ECM). At first sight, the activities of proteinases that can degrade matrix, such as matrix metalloproteinases (MMPs), might be expected to be under-expressed in fibrosis or, if present, could function to resolve the excess matrix. However, as we review here, some MMPs are indeed anti-fibrotic, whereas others can have pro-fibrotic functions. MMPs modulate a range of biological processes, especially processes related to immunity and tissue repair and/or remodeling. Although we do not yet know precisely how MMPs function during fibrosis--that is, the protein substrate or substrates that an individual MMP acts on to effect a specific process--experiments in mouse models demonstrate that MMP-dependent functions during fibrosis are not limited to effects on ECM turnover. Rather, data from diverse models indicate that these proteinases influence cellular activities as varied as proliferation and survival, gene expression, and multiple aspects of inflammation that, in turn, impact outcomes related to fibrosis.
Center for Lung Biology, University of Washington, Seattle, WA 98122, USA.
Matthew
M
Giannandrea
William C
WC
Parks
D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009928:Organ Specificity
D020782:Matrix Metalloproteinases
Collagen; Extracellular matrix; Fibrosis; Metalloproteinase; TIMP