Abstract
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.
Highlights
Various epigenetic mechanisms: DNA methylation, histone acetylation/methylation, and alterations in small non-coding RNAs can influence the expression of Matrix metalloproteinases (MMPs), tissue inhibitors of MMPs, and the transcription factors that regulate the expression of MMPs (Table 1)
Prevalent diseases and commonly prescribed medicinal drugs can introduce epigenetic pressure through these mechanisms to alter the proteolytic activity of MMPs
Our understanding of human conditions associated with alterations in the proteolytic activity of MMPs must consider that these conditions and their medicinal treatments are potential causes of epigenetics-related alterations in MMP activity
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Quantifiable epigenetic mechanisms of gene regulation involve chemical modifications on DNA (such as methylation) and DNA-bound histone proteins (such as methylation or acetylation of histone tails) [3]. The. N-terminal tails of core histones are accessible to post-translational modifications, which can influence gene expression by facilitating or hindering the access of transcription factors and enzymes to the DNA promoter regions [6,7,8] (Figure 1). N-terminal tails of core histones are accessible to post-translational modifications, which can influence gene expression by facilitating or hindering the access of transcription factors and enzymes to the DNA promoter regions [6,7,8] (Figure 1) These modifications include but are not limited to methylation, acetylation, and phosphorylation [9]. The possible involvement of epigenetic mechanisms in the causation of aberrant MMP activity in the settings of acute and chronic diseases and in response to common medicinal drugs is important for predicting disease development and progression, as well as for designing more efficacious therapeutic interventions
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