Regulation of tissue injury responses by the exposure of matricryptic sites within extracellular matrix molecules

Abstract

Extracellular matrix (ECM) is known to provide signals controlling cell shape, migration, proliferation, differentiation, morphogenesis, and survival. Recent data shows that some of these signals are derived from biologically active cryptic sites within matrix molecules (matricryptic sites) that are revealed after structural or conformational alteration of these molecules. We propose the name, matricryptins, for enzymatic fragments of ECM containing exposed matricryptic sites. Mechanisms regulating the exposure of matricryptic sites within ECM molecules include the major mechanism of enzymatic breakdown as well as others including ECM protein multimerization, adsorption to other molecules, cell-mediated mechanical forces, and ECM denaturation. Such matrix alterations occur during or as a result of tissue injury, and thus, the appearance of matricryptic sites within an injury site may provide important new signals to regulate the repair process. Here, we review the data supporting this concept and provide insight into why the increased exposure of matricryptic sites may be an important regulatory step in tissue responses to injury.

Figure 1.

Schematic diagram illustrating how tissue injury leads to the generation of matricryptic sites and matricryptins which participate in the regulation of key aspects of tissue injury responses. FN, fibronectin; VN, vitronectin; FBG, fibrinogen; OPN, osteopontin; LM, laminin; TSP, thrombospondin.

Figure 2.

Mechanisms for the generation of matricryptic sites during tissue injury responses. Individual ECM proteins and known mechanisms for the generation of matricryptic sites are indicated.

Figure 3.

Generation of RGD-containing matricryptic sites and matricryptins from collagen type I regulates arteriolar vasomotor activity.