Revisiting the matricellular concept

Abstract

The concept of a matricellular protein was first proposed by Paul Bornstein in the mid-1990s to account for the non-lethal phenotypes of mice with inactivated genes encoding thrombospondin-1, tenascin-C, or SPARC. It was also recognized that these extracellular matrix proteins were primarily counter or de-adhesive. This review reappraises the matricellular concept after nearly two decades of continuous investigation. The expanded matricellular family as well as the diverse and often unexpected functions, cellular location, and interacting partners/receptors of matricellular proteins are considered. Development of therapeutic strategies that target matricellular proteins are discussed in the context of pathology and regenerative medicine.

Embracing the complexity of matricellular proteins: the functional and clinical significance of splice variation

“…Examples of matricellular proteins include the secreted protein acidic and rich in cysteine (SPARC) family, thrombospondins, tenascins, osteopontin (OPN), the CCN family and periostin (POSTN). Although distinguished from structural matrix proteins such as collagen they nevertheless play an essential regulatory role, and are typically induced during tissue remodelling and repair as well as in many disease states (5). Matricellular proteins can influence matrix formation.…”

“…In terms of integrin binding, most matricelllar proteins bind to multiple integrin receptors, for example, SPARC, CCN1, OPN, POSTN and fibulin-5 (5). Matricellular proteins can therefore directly regulate cell-matrix interactions with subsequent effects on cell adhesion and migration.…”

“…The specific molecular mechanisms underlying this context dependence are almost entirely unknown, yet this must be addressed if we are to harness the potential therapeutic value of these powerful regulatory proteins. A number of matricellular proteins are currently involved in clinical trials (5,47), and it will therefore be important that we better understand the mechanisms behind their controversial effects.…”

“…However, the expression of alternate transcripts for the matricellular family has been reported for only a handful of genes (5). In this review we will examine for the first time the evidence for alternative splicing across the matricellular family, highlighting specific areas for further study.…”

Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer

“…Phenotypes of null mutants may only become evident when mice are subjected to a specific stress that induces matricellular protein expression or signaling. Despite these challenges, studies of matricellular protein function in transgenic mouse models and identification of genetic diseases linked to structural and regulatory mutations in specific matricellular protein genes have proven that they play important roles in physiology and pathophysiology (126,142,171,243).…”