Zhao Xiangyu, Chen Jiayin, Sun Hongxiang, Zhang Yao, Zou Duowu
Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cell Biosci. 2022 Jul 27;12(1):117. doi: 10.1186/s13578-022-00856-w.
Fibrosis is a pathological feature of a variety of chronic inflammatory diseases that can affect almost all organs, which can cause severe consequences and even lead to death. Fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) due to disruption of the balance between ECM production and degradation. Although overabundance of ECM proteins has long been the focus of studies on fibrosis, another facet of the problem-impaired degradation of the ECM-is gaining increasing attention. Matrix metalloproteinase (MMP) and the tissue inhibitor of metalloproteinase (TIMP) system is the main molecular system contributing to ECM degradation, and macrophages are the major regulators of ECM. However, the relationship among macrophages, the MMP/TIMP system and the ECM is not fully understood in the context of fibrosis. Here, we discuss in detail the role played by the ECM in the development of fibrosis and highlight the macrophage-MMP-ECM interaction that is involved in fibrogenesis and may be a potential therapeutic target for fibrosis.
纤维化是多种慢性炎症性疾病的病理特征，几乎可累及所有器官，可导致严重后果甚至死亡。纤维化的特征是细胞外基质（ECM）产生与降解之间的平衡被破坏，导致ECM过度积累。虽然ECM蛋白的过量长期以来一直是纤维化研究的重点，但问题的另一个方面——ECM降解受损——正受到越来越多的关注。基质金属蛋白酶（MMP）和金属蛋白酶组织抑制剂（TIMP）系统是促成ECM降解的主要分子系统，而巨噬细胞是ECM的主要调节因子。然而，在纤维化背景下，巨噬细胞、MMP/TIMP系统与ECM之间的关系尚未完全明确。在此，我们详细讨论ECM在纤维化发展中所起的作用，并强调参与纤维生成且可能成为纤维化潜在治疗靶点的巨噬细胞-MMP-ECM相互作用。
