Stromelysin

Stromelysin is a member of the matrix metalloproteinase (MMP) family, a group of zinc-dependent endoproteases that remodel the extracellular matrix (ECM). The best known form, stromelysin-1, is also referred to as matrix metalloproteinase-3 (MMP-3). Like other MMPs, stromelysin is synthesized as an inactive zymogen and becomes catalytically active after cleavage of its propeptide, with activity tightly regulated in tissues.

Stromelysins degrade a broad range of extracellular substrates. They can break down proteoglycans, laminin, fibronectin, and various collagens, particularly non-fibrillar forms such as type IV collagen. In addition to direct ECM degradation, stromelysin enzymes can activate other proenzymes, including several other MMPs, thereby amplifying matrix breakdown and remodeling in a cascade of proteolytic events.

Regulation and distribution: Expression of stromelysin is induced by cytokines, growth factors, and mechanical stress, and is inhibited by tissue inhibitors of metalloproteinases (TIMPs). It is produced by multiple cell types, including fibroblasts, macrophages, neutrophils, and smooth muscle cells, and is enriched in remodeling or inflammatory tissues.

Clinical and biological significance: Stromelysin participates in normal physiological processes such as tissue remodeling during development and wound healing. It is also involved in pathological conditions including arthritis, periodontitis, osteolysis, and cancer invasion and metastasis. Elevated MMP-3 levels in serum or synovial fluid can reflect disease activity in some inflammatory disorders.

Structure: Stromelysins contain a signal peptide, a propeptide that blocks activity via the cysteine switch, a catalytic metalloproteinase domain with a bound zinc ion, and a hemopexin-like C-terminal domain that influences substrate interactions and inhibitor binding. They are inhibited by TIMPs, particularly TIMP-1 and TIMP-2.