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Revisiting matrix metalloproteinase 12: its role in pathophysiology of asthma and related pulmonary diseases

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CURRENT OPINION IN PULMONARY MEDICINE
卷 27, 期 1, 页码 54-60

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LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MCP.0000000000000743

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asthma; chronic obstructive pulmonary disease; coronavirus disease 2019; matrix metalloproteinase 12; matrix metalloproteinase-12 inhibitor; pulmonary fibrosis

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Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteases with various biological and pathological activities. Increased levels of MMP-12 have been associated with inflammation and structural changes in the lungs in conditions such as asthma, COPD, and pulmonary fibrosis. Targeting MMP-12 may provide further insights into disease mechanisms and potential therapeutic strategies, but further research is needed to fully understand its role in these pulmonary diseases.
Purpose of review Matrix metalloproteinases (MMPs) are a family of over 20 zinc-dependent proteases with different biological and pathological activities, and many have been implicated in several diseases. Although nonselective MMP inhibitors are known to induce serious side-effects, targeting individual MMPs may offer a safer therapeutic potential for several diseases. Hence, we provide a concise overview on MMP-12, given its association with pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, and other progressive pulmonary fibrosis (PPF), which may also occur in coronavirus disease 2019. Recent findings In asthma, COPD, and PPF, increased MMP-12 levels have been associated with inflammation and/or structural changes within the lungs and negatively correlated with functional parameters. Increased pulmonary MMP-12 levels and MMP-12 gene expression have been related to disease severity in asthma and COPD. Targeting MMP-12 showed potential in animal models of pulmonary diseases but human data are still very scarce. Although there may be a potential role of MMP-12 in asthma, COPD and PPF, several pathophysiological aspects await elucidation. Targeting MMP-12 may provide further insights into MMP-12 related mechanisms and how this translates into clinical outcomes; this warrants further research.

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