Matricellular Proteins

Abstract

The term “matricellular” was coined to identify a group of proteins that are secreted and function in the extracellular matrix (ECM), 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, elastin, and fibronectin, and with a number of bioactive proteins, that is, cytokines, growth factors, and proteases, and modify their functions and ECM formation. 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. Nonetheless, the number of proteins that fulfill the above definition is growing. In this article, the structures and diverse biological functions of the core group of matricellular proteins including the thrombospondins, SPARC family members, tenascins, osteopontin, CCN proteins, and fibulins, are considered. Some of the matricellular proteins are not only necessary for the development of lung ECM, but are frequently expressed in pulmonary fibrosis and in neoplasms of the lung, and influence the progress of these disorders.