27.8 : Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.

A collagenase molecule can cleave collagens type I, II, and III at a three-fourths distance from the N-terminal and digest several other ECM and non-ECM molecules.

The expression of MMPs is usually maintained at low levels in the body. Only when required, is MMP's activity modulated for local tissue remodeling. The activity of MMPs is regulated at several levels: regulation of gene expression, controlling the half-life of mRNA, and post-synthesis regulation, using other proteases and inhibitors. The MMPs are regulated by cytokines, growth factors, corticosteroids, retinoic acid, heparin, and interleukin-4.

MMPs help maintain tissue homeostasis and play an essential role in various physiological processes, such as bone remodeling, immunity, angiogenesis, and wound healing.