How Much Do Your Know About MMP 9

How Much Do Your Know About MMP 9 Introduction MMP 9 gene is located in chromosome 20q11.1 ~ 13.1, 26 ~ 27kbp, with 13 exons and 9 introns, belonging to matrix metalloprotein (MMP) family.

Matrix metalloproteinases are a large family named for their requirement of metal ions such as Ca and Zn as cofactors. MMPs can degrade almost all kinds of protein components in the ECM, disrupt the histological barrier of tumor cell invasion, play a key role in tumor invasion and metastasis, and thus are increasingly recognized for their role in tumor invasion and metastasis, and are considered to be the main proteolytic enzymes in this process. The activity of MMPs is regulated at three levels, namely, the level of gene transcription, the activation of inactive enzyme precursors by proteolysis and the action of specific inhibitory factors (TIMPs). Its family members have similar structures and generally consist of five functionally distinct domains.

Family Member At present, 26 members of the MMPs family have been isolated and identified, numbered MMP1 to 26, respectively. Based on the substrate and fragment homology, MMPs are classified into six groups, which are collagenases, gelatinases, stromelysins, stromelysins, furin-activated MMPs, and other secreted MMPs. Type IV collagenase is an important group among them, and it has two main forms, one is glycated and has a molecular weight of 92 kD and is named MMP 9; the other is non-glycated and has a molecular weight of 72 kD and is called MMP 2. At present, the research on MMP 2 and MMP 9 is deeper.

Structure and Function The main function of MMP 9 is to degrade and remodel the homeostasis of the extracellular matrix. Mammalian MMP 9 mRNA has approximately 80% homology. The promoter region of MMP 9 contains activating protein (AP) -1, AP-2, and stimulatory protein (SP) -1 factor binding sites, and the porcine MMP 9 promoter region also has nuclear factor (NF) κB, ETS binding sites, and transforming growth factor (TGF)-β inhibitory elements.

In addition to the prototypical structure of MMPs, the catalytic region of MMP 9 includes three repeating fibronectin domains, which have a high affinity for gelatin or elastin. MMP 9 contains a type V collagen domain, which is highly glycosylated, and it influences substrate specificity and has anti-decay properties. There are many substrates for MMP 9, such as collagen IV, V, VII, X, and XI, core protein of proteoglycans, gelatin, fibronectin, laminin, and elastin, and cytokines and their receptors are also substrates for MMP 9 action.

MMP 9 is secreted from the cytoplasm to the extracellular space in the form of zymogen. In vitro, MMP 9 is only active through the reaction of organic mercury preparations, and in vivo, it can be activated through a series of protease cascades. This collagen domain can be cleaved

by MMP 3, MMP 2, or hypochlorous acid, but not by plasmin, thrombin, or MMP 1. MMP 3 may

be the most potent activator of MMP 9. The major circulating inhibitor of MMP 9 is 2 macroglobulin, and activated MMP 9 is captured by 2 macroglobulin and removed from the circulatory system by clearance of the receptor.

Tissue inhibitors of metalloproteinases (TIMPs) are a family of tissue inhibitors of MMPs that are widely distributed in tissues and body fluids and inhibit their activity by covalently binding to MMPs. TIMP 1, as an inhibitor of MMP 9, specifically binds to the carboxyl terminus of the zymogen or catalytic region of the activated enzyme of MMP 9 and forms a complex, thereby specifically inhibiting the activity of MMP 9. In addition, MMP-9 activity was also inhibited by thrombospondin and tissue inhibitor of protease 2 (TFPI-2).

MMP 9 can break down structural complexes in the respiratory tract and lungs, such as the ECM and basement membrane, and thus can participate in respiratory tract and lung remodeling. It can also regulate the activity of other proteases and cytokines.

Furthermore, MMP 9 binding to CD44 releases stored TGF-β1 and additionally, MMP 9 can participate in angiogenesis by releasing vascular endothelial growth factor (VEGF).