Periostin as a Multifunctional Modulator of the Wound Healing Response

Abstract

During tissue healing, dynamic and temporal alterations occur in the structure and composition of the extracellular matrix (ECM) that are required for effective repair to occur. Matricellular proteins (MPs) are a group of diverse non-structural ECM components, which bind cell surface receptors mediating interactions between the cell and its microenviroment, effectively regulating adhesion, migration, proliferation, signaling and cell phenotype. Periostin (Postn), a pro-fibrogenic secreted glycoprotein, was defined as a MP based on its expression pattern and regulatory roles during development, healing and in disease processes. Postn consists of a typical signal sequence, an EMI domain responsible for binding to fibronectin, four tandem fasciclin-like domains that are responsible for integrin binding and a C-terminal region where multiple splice variants originate. This review will focus specifically on the role of Postn in wound healing and remodeling, an area of intense research in the last 10 years particularly related to skin healing as well as in myocardium post infarction. Postn interacts with cells through various integrin pairs and is an essential downstream effector of TGF-β superfamily signaling. As will be discussed, across different tissues, Postn is associated with pro-fibrogenic process, specifically, the transition of fibroblasts to myofibroblasts, collagen fibrillogenesis and ECM synthesis. Although the complexity of Postn as a modulator of cell behavior in tissue healing is only beginning to be elucidated, its expression is clearly a defining event in moving wound healing through the proliferative and remodeling phases.