Extracellular matrix-derived peptides in tissue remodeling and fibrosis

Abstract

Alterations in the composition of the extracellular matrix (ECM) critically regulate the cellular responses in tissue repair, remodeling, and fibrosis. After injury, proteolytic degradation of ECM generates bioactive ECM fragments, named matricryptins, exposing cryptic sites with actions distinct from the parent molecule. Matricryptins contribute to the regulation of inflammatory, reparative, and fibrogenic cascades through effects on several different cell types both in acute and chronic settings. Fibroblasts play a major role in matricryptin generation not only as the main cellular source of ECM proteins, but also as producers of matrix-degrading proteases. Moreover, several matricryptins exert fibrogenic or reparative actions by modulating fibroblast phenotype and function. This review manuscript focuses on the mechanisms of matricyptin generation in injured and remodeling tissues with an emphasis on fibroblast-matricryptin interactions.

Keywords: Extracellular matrix; Fibroblasts; Fibrosis; Matricryptins; Peptides; Remodeling.

Figure 1.

Effects of matricryptins in tissue fibrosis. Following tissue injury, proteolytic degradation of ECM proteins generates a wide range of matricryptins that may participate in the pathogenesis of fibrosis, either directly, through actions on steady state fibroblasts (FIB), that can become activated and differentiate into a myofibroblast (MF), or indirectly by recruiting or activating inflammatory cells (N, neutrophil; M, monocyte) and endothelial cells (EC).