Abstract：
Fibrosis is a process of tissue repair that results in the slow creation of scar tissue to replace healthy tissue and can affect any tissue or organ. Its primary feature is the massive deposition of extracellular matrix (mainly collagen), eventually leading to tissue dysfunction and organ failure. The progression of fibrotic diseases has put a significant strain on global health and the economy, and as a result, there is an urgent need to find some new therapies. Previous studies have identified that inflammation, oxidative stress, some cytokines, and remodeling play a crucial role in fibrotic diseases and are essential avenues for treating fibrotic diseases. Among them, matrix metalloproteinases (MMPs) are considered the main targets for the treatment of fibrotic diseases since they are the primary driver involved in ECM degradation, and tissue inhibitors of metalloproteinases (TIMPs) are natural endogenous inhibitors of MMPs. Through previous studies, we found that MMP-9 is an essential target for treating fibrotic diseases. However, it is worth noting that MMP-9 plays a bidirectional regulatory role in different fibrotic diseases or different stages of the same fibrotic disease. Previously identified MMP-9 inhibitors, such as pirfenidone and nintedanib, suffer from some rather pronounced side effects, and therefore, there is an urgent need to investigate new drugs. In this review, we explore the mechanism of action and signaling pathways of MMP-9 in different tissues and organs, hoping to provide some ideas for developing safer and more effective biologics.
摘要：
纤维化是组织修复过程,其导致瘢痕组织的缓慢产生以替代健康组织并且可以影响任何组织或器官。其主要特征是大量沉积细胞外基质（主要是胶原蛋白），最终导致组织功能障碍和器官衰竭。纤维化疾病的进展给全球健康和经济带来了巨大的压力。结果，迫切需要找到一些新的治疗方法。以前的研究已经确定炎症，氧化应激，一些细胞因子，和重塑在纤维化疾病中起着至关重要的作用，并且是治疗纤维化疾病的重要途径。其中,基质金属蛋白酶（MMPs）被认为是治疗纤维化疾病的主要靶标，因为它们是参与ECM降解的主要驱动因素。金属蛋白酶的组织抑制剂(TIMPs)是MMP的天然内源性抑制剂。通过以往的研究,我们发现MMP-9是治疗纤维化疾病的重要靶点.然而,值得注意的是，MMP-9在不同纤维化疾病或同一纤维化疾病的不同阶段发挥双向调节作用。以前发现的MMP-9抑制剂，比如吡非尼酮和尼达尼布，有一些相当明显的副作用，因此,迫切需要研究新药。在这次审查中,探讨MMP-9在不同组织器官中的作用机制和信号通路,希望为开发更安全、更有效的生物制剂提供一些思路。
