Tissue Inhibitor of Metalloproteinase (TIMP)
A family of proteins that inhibit matrix metalloproteinases, maintaining the balance between ECM synthesis and degradation. The MMP/TIMP balance is critical for normal tissue remodelling during wound healing and is disrupted in conditions involving excessive tissue destruction or fibrosis.
Technical Context
Four TIMPs (TIMP-1, -2, -3, -4) inhibit MMPs by binding in a 1:1 stoichiometric complex to the MMP active site zinc. Each TIMP has a somewhat different MMP inhibition profile: TIMP-1 preferentially inhibits MMP-9 and most soluble MMPs; TIMP-2 inhibits MMP-2 (but also paradoxically activates pro-MMP-2 in complex with MT1-MMP at low concentrations); TIMP-3 is the broadest spectrum inhibitor (also inhibits ADAMs — a disintegrin and metalloproteinases); TIMP-4 is predominantly cardiac. Beyond MMP inhibition, TIMPs have growth factor-like activities: TIMP-1 promotes cell proliferation, TIMP-2 inhibits endothelial cell proliferation (anti-angiogenic). In chronic non-healing wounds, the MMP/TIMP ratio is elevated (excessive MMP activity degrades newly deposited matrix faster than it can accumulate); in fibrotic conditions, the ratio is reduced (insufficient MMP activity allows excessive collagen accumulation).