Abstract：
Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality globally and the risk of developing lung cancer is six times greater in individuals with COPD who smoke compared to those who do not smoke. Matrix metalloproteinases (MMPs) play a crucial role in the pathophysiology of respiratory diseases by promoting inflammation and tissue degradation. Furthermore, MMPs are involved in key processes like epithelial-to-mesenchymal transition (EMT), metastasis, and invasion in lung cancer. While EMT has traditionally been associated with the progression of lung cancer, recent research highlights its active involvement in individuals with COPD. Current evidence underscores its role in orchestrating airway remodeling, fostering airway fibrosis, and contributing to the potential for malignant transformation in the complex pathophysiology of COPD. The precise regulatory roles of diverse MMPs in steering EMT during COPD progression needs to be elucidated. Additionally, the less-understood aspect involves how these MMPs bi-directionally activate or regulate various EMT-associated signaling cascades during COPD progression. This review article explores recent advancements in understanding MMPs\' role in EMT during COPD progression and various pharmacological approaches to target MMPs. It also delves into the limitations of current MMP inhibitors and explores novel, advanced strategies for inhibiting MMPs, potentially offering new avenues for treating respiratory diseases.
摘要：
慢性阻塞性肺疾病（COPD）是全球第三大死亡原因，吸烟的COPD患者患肺癌的风险是不吸烟的人的六倍。基质金属蛋白酶（MMPs）通过促进炎症和组织降解，在呼吸系统疾病的病理生理中起着至关重要的作用。此外，MMP参与关键过程，如上皮-间质转化（EMT），转移,和肺癌的侵袭。虽然EMT传统上与肺癌的进展有关，最近的研究强调了其在COPD患者中的积极参与。目前的证据强调了它在协调气道重塑中的作用，促进气道纤维化，并有助于COPD复杂病理生理学中的恶性转化。需要阐明不同MMPs在COPD进展过程中指导EMT的精确调节作用。此外,较少理解的方面涉及这些MMP如何在COPD进展期间双向激活或调节各种EMT相关信号级联。这篇综述文章探讨了在COPD进展过程中了解MMPs在EMT中的作用以及靶向MMPs的各种药理学方法的最新进展。它还深入研究了当前MMP抑制剂的局限性，并探索了新的，抑制MMPs的先进策略，可能为治疗呼吸系统疾病提供新的途径。
