Matrikines and the lungs.

The extracellular matrix is a complex network of fibrous and nonfibrous molecules that not only provide structure to the lung but also interact with and regulate the behaviour of the cells which it surrounds. Recently it has been recognised that components of the extracellular matrix proteins are released, often through the action of endogenous proteases, and these fragments are termed matrikines. Matrikines have biological activities, independent of their role within the extracellular matrix structure, which may play important roles in the lung in health and disease pathology. Integrins are the primary cell surface receptors, characterised to date, which are used by the matrikines to exert their effects on cells. However, evidence is emerging for the need for co-factors and other receptors for the matrikines to exert their effects on cells. The potential for matrikines, and peptides derived from these extracellular matrix protein fragments, as therapeutic agents has recently been recognised. The natural role of these matrikines (including inhibitors of angiogenesis and possibly inflammation) make them ideal targets to mimic as therapies. A number of these peptides have been taken forward into clinical trials. The focus of this review will be to summarise our current understanding of the role, and potential for highly relevant actions, of matrikines in lung health and disease.