Journal
BIOMOLECULES
Volume 11, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/biom11040578
Keywords
MMP; epigenetics; cancer; cardiovascular disease; statins; tetracyclines; bone disease; tuberculosis; COVID-19
Categories
Funding
- Natural Sciences and Engineering Council of Canada [RES0034250]
- University of Alberta Hospital Foundation for Medical Research [RES0048483]
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Matrix metalloproteinases (MMPs) play a crucial role in organ development, function, and cellular responses to diseases and drugs, while various diseases and drugs can alter MMP activity through different mechanisms. These pathologies and medications may also exert epigenetic pressure on the expression of MMP genes.
Matrix metalloproteinases (MMPs) cleave extracellular matrix proteins, growth factors, cytokines, and receptors to influence organ development, architecture, function, and the systemic and cell-specific responses to diseases and pharmacological drugs. Conversely, many diseases (such as atherosclerosis, arthritis, bacterial infections (tuberculosis), viral infections (COVID-19), and cancer), cholesterol-lowering drugs (such as statins), and tetracycline-class antibiotics (such as doxycycline) alter MMP activity through transcriptional, translational, and post-translational mechanisms. In this review, we summarize evidence that the aforementioned diseases and drugs exert significant epigenetic pressure on genes encoding MMPs, tissue inhibitors of MMPs, and factors that transcriptionally regulate the expression of MMPs. Our understanding of human pathologies associated with alterations in the proteolytic activity of MMPs must consider that these pathologies and their medicinal treatments may impose epigenetic pressure on the expression of MMP genes. Whether the epigenetic mechanisms affecting the activity of MMPs can be therapeutically targeted warrants further research.
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