Periostin promotes a fibroblastic lineage pathway in atrioventricular valve progenitor cells
Open Access
- 30 March 2009
- journal article
- research article
- Published by Wiley in Developmental Dynamics
- Vol. 238 (5), 1052-1063
- https://doi.org/10.1002/dvdy.21933
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 TGFβ‐3. We further demonstrate that TGFβ‐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 TGFβ‐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). Developmental Dynamics 238:1052–1063, 2009.Keywords
This publication has 85 references indexed in Scilit:
- Temporal and spatial expression of collagens during murine atrioventricular heart valve development and maintenanceDevelopmental Dynamics, 2008
- An absence of Twist1 results in aberrant cardiac neural crest morphogenesisDevelopmental Biology, 2008
- Periostin regulates atrioventricular valve maturationDevelopmental Biology, 2008
- BMP-2 induces cell migration and periostin expression during atrioventricular valvulogenesisDevelopmental Biology, 2008
- Periostin is essential for cardiac healingafter acute myocardial infarctionThe Journal of Experimental Medicine, 2008
- Tbx20 regulation of endocardial cushion cell proliferation and extracellular matrix gene expressionDevelopmental Biology, 2007
- Periostin promotes atrioventricular mesenchyme matrix invasion and remodeling mediated by integrin signaling through Rho/PI 3-kinaseDevelopmental Biology, 2007
- Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissuesJournal of Cellular Biochemistry, 2007
- Mutations in NOTCH1 cause aortic valve diseaseNature, 2005
- A series of normal stages in the development of the chick embryoDevelopmental Dynamics, 1992