MMP1

MMP1, or matrix metalloproteinase-1, is a human gene that encodes collagenase-1, a zinc-dependent endopeptidase in the matrix metalloproteinase (MMP) family. The enzyme plays a central role in remodeling and turnover of the extracellular matrix (ECM) and is expressed by various cell types, including fibroblasts, macrophages, and chondrocytes.

MMP-1 is produced as an inactive zymogen, pro-MMP-1, and requires proteolytic activation to become catalytically active. Activation is achieved by other proteases such as MMP-3 or plasmin. The mature enzyme contains a catalytic domain that coordinates a zinc ion and a C-terminal hemopexin-like domain that influences substrate specificity. Its principal substrates are native fibrillar collagens types I, II, and III, making it a key mediator of ECM degradation and tissue remodeling.

Expression and activity of MMP-1 are tightly regulated at the transcriptional and post-translational levels. Cytokines and growth factors, including interleukin-1 and tumor necrosis factor, can upregulate MMP-1 expression, while tissue inhibitors of metalloproteinases (TIMPs) help restrain activity. The regulation also involves transcription factors such as AP-1 and is influenced by mechanical stress.

Physiological roles include normal development, wound healing, and turnover of connective tissue. Pathologically, dysregulated MMP-1 activity contributes to joint destruction in osteoarthritis and rheumatoid arthritis and can facilitate cancer cell invasion by breaking down ECM barriers. Clinically, elevated MMP-1 levels have been explored as biomarkers in certain diseases, and MMP inhibitors have been investigated as therapeutic agents, though clinical success has been limited by side effects and broad inhibition of the MMP family.

The MMP1 gene is located on chromosome 11 and is also referred to as collagenase-1.