- Matrix metalloproteinase-3 (MMP-3), also known as stromelysin-1, is a member of the matrix metalloproteinase family—enzymes responsible for the degradation and remodeling of the extracellular matrix (ECM).
- MMP-3 is secreted as an inactive zymogen (pro-MMP-3) and becomes enzymatically active only after proteolytic cleavage.
- Structurally, MMP-3 consists of a pro-domain that maintains the enzyme in an inactive form, a catalytic domain containing a zinc-binding motif essential for its proteolytic activity, and a hemopexin-like domain involved in substrate recognition and interactions with tissue inhibitors of metalloproteinases (TIMPs).
- Functionally, MMP-3 plays a central role in ECM degradation. It is capable of breaking down a wide range of ECM components including collagens (types II, III, IV, IX, and X), fibronectin, laminin, and proteoglycans. Beyond direct matrix degradation, MMP-3 also activates other MMPs—such as MMP-1, MMP-7, and MMP-9—thereby amplifying ECM remodeling. This makes MMP-3 a critical player in tissue repair, wound healing, angiogenesis, and developmental processes. Additionally, MMP-3 influences cell behavior and signaling by modulating molecules involved in cell adhesion and by participating in epithelial-to-mesenchymal transition (EMT), a key process in cancer metastasis. It has also been linked to activation of the β-catenin signaling pathway, further contributing to cell proliferation and transformation.
- In terms of disease, overexpression of MMP-3 has been associated with various pathological conditions. In cancer, MMP-3 promotes tumor invasion, metastasis, and neovascularization. In rheumatoid arthritis, it contributes to the breakdown of joint cartilage. In cardiovascular disease, MMP-3 plays a role in destabilizing atherosclerotic plaques. Notably, during Helicobacter pylori infection, MMP-3 is upregulated in gastric epithelial cells, particularly in response to the CagA oncoprotein. This induction contributes to chronic inflammation, tissue damage, and potentially to gastric carcinogenesis.
- MMP-3 expression is regulated by various stimuli, including pro-inflammatory cytokines (such as IL-1β and TNF-α), growth factors, and bacterial infections. Its activity is kept in check by tissue inhibitors of metalloproteinases (TIMPs), particularly TIMP-1 and TIMP-2, which bind active MMPs and prevent excessive tissue degradation. The balance between MMPs and TIMPs is critical for maintaining tissue homeostasis, and its disruption can lead to pathological remodeling and disease.
