EXTRACELLULAR MATRIX | Matricellular Proteins

Abstract

The term ‘matricellular’ was coined to identify a group of proteins that are secreted and function in the extracellular matrix, but do not play a structural role as an integral component of a physical entity such as a fiber or basement membrane. Instead, matricellular proteins primarily serve to modulate cell function. These functions are achieved in part by interaction with a variety of cell-surface receptors, with the resulting engagement of signal transduction pathways. Matricellular proteins are also capable of interacting with structural matrix proteins, such as collagens and fibronectin, and with a number of bioactive proteins, that is, cytokines, growth factors, and proteases. As a consequence, these bioactive molecules can either be sequestered in the matrix, presented to their appropriate receptors, or in the case of proteases, inhibited by direct binding or cleared from the pericellular environment by formation of protein–enzyme complexes that are recognized by a scavenger receptor. It should be noted, however, that the distinction between matricellular and structural matrix proteins is not sharp, since structural proteins such as collagens, laminins, and fibronectin also influence cell function by interaction with cell-surface receptors, and they also bind bioactive proteins. The classification of proteins as matricellular is based on similarity of mode of action rather than on homology in amino acid sequence and three-dimensional structure. Thus, the thrombospondins, SPARC family members, tenascins, CCN proteins, and osteopontin, the core group of matricellular proteins considered in this chapter, are structurally unrelated. The partial dependence of the function of matricellular proteins on the proteins with which they interact gives rise to the characterization of their function as contextual. The relevance of these proteins to the biochemistry and physiology of the lung will therefore depend to a large extent on the co-expression of interacting proteins. Matricellular proteins are frequently expressed in pulmonary fibrosis and in neoplasms of the lung, and early evidence supports the ability of these proteins to influence the progress of these disorders.