Advances in the Role of the Extracellular Matrix in Development and Disease

Abstract

Almost all cells in multi-cellular organisms contact, on at least one of their surfaces, an intricate meshwork of interacting extracellular molecules that constitute the extracellular matrix. The amount and type of extracellular matrix is highly variable especially during development, and is tissue dependent (1). The complexity of the molecules within the extracellular matrix is beginning to be realized with the identification of various gene families and their roles in acquired and genetic diseases. There is considerable evidence that the extracellular matrix has many structural and biological functions in tissues. Much of the information on the biological activity of the extracellular matrix has come from in vitro studies with cells grown on purified matrices and on isolated components, and from the elucidation of the role of matrix molecules in diseases (Table 1) (2–4). Many of the acquired diseases are due to autoantibodies to extracellular matrix, such as Goodpasture’s syndrome and glomerular nephritis, or to accumulation of too much or of the wrong type of matrix material, such as diabetes and arthritis. Others diseases are genetic and involve mutations and deletions, such as Ehlers-Danlos and osteogenesis imperfecta. The importance of the extracellular matix in development is confirmed with the various genetic diseases. Also the biochemistry of these molecules is beginning to be understood at the structural level and active sites have been identified using fragments, antibodies and synthetic peptides. Because of their important biological activities, some of these extracellular matrix molecules have the potential to be used therapeutically for tissue repair and possibly control of disease progression.