title: Periostin promotes a fibroblastic lineage pathway in atrioventricular valve progenitor cells.
abstract: Differentiation of prevalvular mesenchyme into valve fibroblasts is an integral step towards the development of functionally mature cardiac valves. Although clinically relevant, little is known regarding the molecular and cellular mechanisms by which this process proceeds. Genes that are regulated in a spatio-temporal pattern during valve remodeling are candidates for affecting this differentiation process. Based on its expression pattern, we have focused our studies on the role of the matricellular gene, periostin, in regulating the differentiation of cushion mesenchymal cells into valve fibroblasts. Herein, we demonstrate that periostin expression is coincident with and regulates type I collagen protein production, a major component of mature valve tissue. Adenoviral-mediated knock-down of periostin in atrioventricular mesenchyme resulted in a decrease in collagen I protein expression and aberrant induction of myocyte markers indicating an alteration in AV mesenchyme differentiation. In vitro analyses using a novel "cardiotube" assay further demonstrated that expression of periostin regulates lineage commitment of valve precursor cells. In these cells, expression of periostin and collagen I are regulated, in part, by TGFbeta-3. We further demonstrate that TGFbeta-3, through a periostin/collagen pathway, enhances the viscoelastic properties of AV cushion tissue surface tension and plays a crucial role in regulating valve remodeling. Thus, data presented here demonstrate that periostin, a TGFbeta-3 responsive gene, functions as a crucial mediator of chick AV valve maturation via promoting mesenchymal-to-fibroblast differentiation while blocking differentiation of alternative cell types (myocytes).
authors.affiliation: Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina 29425, USA. norrisra@musc.edu
authors.forename: Russell A
authors.initials: RA
authors.lastname: Norris
authors.forename: Jay D
authors.initials: JD
authors.lastname: Potts
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yost
authors.forename: Lorain
authors.initials: L
authors.lastname: Junor
authors.forename: Tim
authors.initials: T
authors.lastname: Brooks
authors.forename: Hong
authors.initials: H
authors.lastname: Tan
authors.forename: Stanley
authors.initials: S
authors.lastname: Hoffman
authors.forename: Mary M
authors.initials: MM
authors.lastname: Hart
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kern
authors.forename: Brooke
authors.initials: B
authors.lastname: Damon
authors.forename: Roger R
authors.initials: RR
authors.lastname: Markwald
authors.forename: Richard L
authors.initials: RL
authors.lastname: Goodwin