Matrix metalloproteinases (MMPs) are a family of enzymes that break down the extracellular matrix (ECM), the structural scaffolding that supports cells and tissues. This process of degradation is essential for tissue remodeling. Matrix Metalloproteinase-7 (MMP7), also known as Matrilysin, is the smallest member of this family. Its actions are highly regulated, but when this regulation fails, MMP7’s activity can shift from necessary maintenance to destructive pathology. Understanding Matrilysin’s dual nature—as both a constructive and destructive force—is key to grasping its profound impact on human health.
MMP7: An Overview of Structure and Function
MMP7 is structurally unique within the metalloproteinase family because it lacks a hemopexin domain, a feature present in most other MMPs. This absence makes it a much smaller enzyme, typically around 30 kDa in its inactive precursor form. Like all MMPs, Matrilysin is a zinc-dependent endopeptidase, meaning it requires a zinc ion at its active site to cleave peptide bonds. It is initially secreted as an inactive pro-enzyme and must undergo a proteolytic cleavage to become fully active.
The active enzyme then targets and degrades numerous components of the ECM, including macromolecules like fibronectin, laminin, and specific types of collagen. This broad substrate specificity allows MMP7 to efficiently clear old or damaged matrix material, a process fundamental to tissue maintenance and repair. Beyond the ECM, MMP7 also processes non-matrix proteins, such as pro-enzymes and growth factors, thereby modulating the activity of other signaling molecules.
MMP7’s Role in Healthy Tissue Turnover
In a healthy body, MMP7’s activity is tightly controlled and serves beneficial physiological functions, primarily centered on tissue remodeling and defense. It is highly expressed by epithelial cells in the intestines, lungs, and skin, where it is instrumental in maintaining the integrity of these barrier tissues. This involves the constant turnover of the basement membrane, the specialized ECM layer that anchors epithelial cells, ensuring cell migration and proper organization.
Matrilysin is also a key player in wound healing. By degrading the provisional matrix and clearing debris at the injury site, the enzyme creates a path for new cells, such as keratinocytes, to migrate and close the wound. Furthermore, MMP7 has a specialized, non-matrix-degrading role in the innate immune system. It proteolytically activates precursor molecules like pro-defensins into their mature, antimicrobial forms, providing a first line of defense against invading pathogens. The enzyme also acts to liberate growth factors sequestered within the ECM, stimulating cell proliferation and tissue growth necessary for repair.
Contribution to Pathological Processes
The beneficial activity of MMP7 becomes destructive when its expression or activation is dysregulated, leading to pathological conditions. This enzyme is heavily implicated in cancer progression, where its matrix-degrading power facilitates the spread of malignant cells. Overexpression of MMP7 allows tumor cells to break down the basement membrane barrier, which is a prerequisite for local invasion and distant metastasis.
The enzyme’s activity also contributes to tumor growth by processing cell adhesion molecules. MMP7 can cleave E-cadherin, a protein responsible for holding epithelial cells together. This cleavage loosens cell-to-cell bonds and promotes the detachment of cancer cells from the primary tumor. This E-cadherin cleavage is a step in the process known as Epithelial-Mesenchymal Transition (EMT), which gives cancer cells a more migratory and invasive phenotype. Elevated MMP7 levels are associated with a poor prognosis in various tumors, including those of the digestive tract and breast.
Beyond cancer, MMP7 contributes to chronic inflammatory and fibrotic diseases, such as interstitial lung disease and kidney fibrosis. In these conditions, the uncontrolled, excessive degradation of the ECM leads to permanent tissue damage and scarring, disrupting normal organ architecture. For example, in rheumatoid arthritis-associated interstitial lung disease, MMP7 mediates the synthesis of excess collagen, which results in the thickening and stiffening of lung tissue. This destructive cycle highlights the difference between the enzyme’s normal, transient remodeling activity and its sustained, pathological overdrive.
MMP7 as a Biomarker and Therapeutic Target
Given its central role in disease, MMP7 has emerged as a tool for both diagnostics and treatment development. Elevated levels of MMP7 are measured in the blood, urine, or tissue of patients and serve as a prognostic biomarker for several diseases. High MMP7 concentrations, for example, correlate with the severity of liver fibrosis and can predict poor outcomes in various cancers. The ease of measuring this enzyme in bodily fluids makes it an indicator of disease activity and progression.
The destructive nature of Matrilysin in disease also makes it an attractive therapeutic target. Researchers are focused on developing specific inhibitors to block the enzyme’s activity without disrupting the functions of other MMP family members. Early non-selective MMP inhibitors faced challenges because blocking many MMPs simultaneously led to unwanted side effects. However, the development of highly selective, small-molecule inhibitors for MMP7 is an active area of research, with the goal of halting its pathological degradation in fibrotic disorders and metastatic cancer.