Department of Clinical Pharmacology, QPS-Netherlands, Groningen, The Netherlands.
Department of Pediatrics.
Curr Opin Pulm Med. 2021 Jan;27(1):54-60. doi: 10.1097/MCP.0000000000000743.
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.
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.
基质金属蛋白酶（MMPs）是一个锌依赖性蛋白酶家族，具有多种生物学和病理学活性，其中许多与多种疾病有关。尽管已知非选择性 MMP 抑制剂会引起严重的副作用，但针对特定的 MMP 可能为多种疾病提供更安全的治疗潜力。因此，鉴于 MMP-12 与肺部疾病（包括哮喘、慢性阻塞性肺疾病（COPD）、特发性肺纤维化和其他进行性肺纤维化（PPF））有关，我们提供了一个 MMP-12 的简要概述，这些疾病也可能发生在 2019 年冠状病毒病中。
在哮喘、COPD 和 PPF 中，MMP-12 水平的增加与肺部的炎症和/或结构变化有关，并且与功能参数呈负相关。肺部 MMP-12 水平的增加和 MMP-12 基因表达与哮喘和 COPD 的疾病严重程度有关。在肺部疾病的动物模型中，靶向 MMP-12 显示出了一定的潜力，但人类数据仍然非常有限。
尽管 MMP-12 在哮喘、COPD 和 PPF 中可能具有潜在作用，但仍有几个病理生理方面需要阐明。靶向 MMP-12 可能为 MMP-12 相关机制以及如何转化为临床结果提供进一步的见解；这需要进一步的研究。
