title: Periostin promotes atrioventricular mesenchyme matrix invasion and remodeling mediated by integrin signaling through Rho/PI 3-kinase.
abstract: Recent evidence suggests that extracellular matrix components may play a signaling role in embryonic valve development. We have previously identified the spatiotemporal expression patterns of periostin in developing valves, but its function during this process is largely unknown. To evaluate the functional role periostin plays during valvulogenesis, two separate three-dimensional culture assay systems, which model chick atrioventricular cushion development, were employed. These assays demonstrated that cushion mesenchymal cells adhered and spread on purified periostin in a dose-responsive manner, similar to collagen I and fibronectin via alpha(v)beta(3) and beta(1) integrin pairs. Periostin overexpression resulted in enhanced mesenchyme invasion through 3D collagen gels and increased matrix compaction. This invasion was dependent on alpha(v)beta(3) more than beta(1) integrin signaling, and was mediated differentially by Rho kinase and PI 3-kinase. Both matrix invasion and compaction were associated with a colocalization of periostin and beta(1) integrin expression to migratory cell phenotype in both surface and deep cells. The Rho/PI 3-kinase pathway also differentially mediated matrix compaction. Both Rho and PI 3-kinase were involved in normal cushion mesenchyme matrix compaction, but only PI 3-kinase was required for the enhanced matrix compaction due to periostin. Taken together, these results highlight periostin as a mediator of matrix remodeling by cushion mesenchyme towards a mature valve structure.
authors.affiliation: Cardiovascular Developmental Biology Center, Chair of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Butcher
authors.forename: Russell A
authors.initials: RA
authors.lastname: Norris
authors.forename: Stanley
authors.initials: S
authors.lastname: Hoffman
authors.forename: Corey H
authors.initials: CH
authors.lastname: Mjaatvedt
authors.forename: Roger R
authors.initials: RR
authors.lastname: Markwald
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D002642:Chick Embryo; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006351:Heart Valves / Q000196:embryology; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D054460:rho-Associated Kinases
chemical_list: D015815:Cell Adhesion Molecules; D003094:Collagen; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C082838:Postn protein, mouse