Characterisation of matrix metalloproteinase cleavage sites in fibrillin

Fibrillin is the principal structural component of the beaded elastic microfibrils of extracellular matrix (Keene et al. 1991; Kielty & Shuttleworth 1995). Fibrillins are ˜350 kD multidomain glycoproteins with repeating calcium binding epidermal growth factor-like domains interspersed with TB modules (Pereira et al. 1993). Loss of connective tissue elasticity in ageing and disease states may be a result of progressive damage to microfibrils. The matrix metalloproteinases (MMPs) are crucially important in degradation of connective tissue components in tissue development, wound healing, angiogenesis, tumour invasion and metastasis (Parks & Mecham 1993). We have identified 3 major MMP cleavage sites within fibrillin molecules.