The many facets of the matricelluar protein periostin during cardiac development, remodeling, and pathophysiology

Abstract

Periostin is a member of a growing family of matricellular proteins, defined by their ability to interact with components of the extracellular milieu, and with receptors at the cell surface. Through these interactions, periostin has been shown to play a crucial role as a profibrogenic molecule during tissue morphogenesis. Tissues destined to become fibrous structures are dependent on cooperative interactions between periostin and its binding partners, whereas in its absence, these structures either totally or partially fail to become mature fibrous entities. Within the heart, fibrogenic differentiation is required for normal tissue maturation, remodeling and function, as well as in response to a pathological myocardial insult. In this review, aspects related to the function of periostin during cardiac morphogenesis, remodeling and pathology are summarized.

Fig. 1

Expression of periostin in the adult murine tricuspid valve. Immunohistochemical staining of Periostin (green) in the adult murine tricuspid valve leaflet showing robust staining in the chordae tendineae (CT) and valve leaflet. Expression of periostin in non-fibrous tissue (papillary muscle-PM) is negligible

Fig. 2

Periostin molecular regulatory networks in fibroblast progenitor cells. MEKK stimulates TGFβ2 production (I) which is secreted and stimulates its canonical receptor (IIa) This stimulates downstream Smad phosphorylation and activation, which targets these proteins to the nucleus where they cooperate with cell-specific transcription factors to regulate the periostin promoter. It is not known whether these phospho-Smad proteins cooperate with Twist1, YY1, or SRF (known transcriptional regulators of periostin expression) to promote or repress periostin transcription. BMP2/4 (IIb) are known to act through the Smad 1/5/8 pathway to activate Twist1 and stimulate periostin expression. Periostin is secreted, after which it can interact with specific-cell surface receptors (III). In doing so, they stimulate intracellular signal cascades which involve, among other, PI3-Kinase and Rho kinase. This stimulates filipodia and actin reorganization (stress fiber formation) to mediate migration, adhesion, and fibroblast differentiation. Secreted periostin additionally regulates collagen fibrillogenesis via a promotion of collagen cross-linking (IV). Through these combined matricellular functions (receptor-mediated cell signaling and matrix interactions), periostin regulates the differentiation, maturation, and biomechanical properties of connective tissues, including skin, tendon, and heart valves