Periostin and TGF-β-induced protein: Two peas in a pod?

Periostin (PN) and TGF-β-induced protein (βig-h3) are paralogs that contain a single emilin and four fasciclin-1 modules and are secreted from cells. PN receives attention because of its up-regulation in cancer and degenerative and allergic diseases. βig-h3 is highly enriched in cornea and best known for harboring mutations in humans associated with corneal dystrophies. Both proteins are expressed widely, and many functions, some over-lapping, have been attributed to PN and βig-h3 based on biochemical, cell culture, and whole animal experiments. We attempt to organize this knowledge so as to facilitate research on these interesting and incompletely understood proteins. We focus particularly on whether PN and βig-h3 are modified by vitamin K-dependent γ-glutamyl carboxylation, a question of considerable importance given the profound effects of γ-carboxylation on structure and function of other proteins. We consider the roles of PN and βig-h3 in formation of extracellular matrix and as ligands for integrin receptors. We attempt to reconcile the contradictory results that have arisen concerning the role of PN, which has emerged as a marker of TH2 immunity, in murine models of allergic asthma. Finally, when possible we compare and contrast the structures and functions of the two proteins.