title: Transforming growth factor Beta2 is required for valve remodeling during heart development.
abstract: Although the function of transforming growth factor beta2 (TGFβ2) in epithelial mesenchymal transition (EMT) is well studied, its role in valve remodeling remains to be fully explored. Here, we used histological, morphometric, immunohistochemical and molecular approaches and showed that significant dysregulation of major extracellular matrix (ECM) components contributed to valve remodeling defects in Tgfb2(-/-) embryos. The data indicated that cushion mesenchymal cell differentiation was impaired in Tgfb2(-/-) embryos. Hyaluronan and cartilage link protein-1 (CRTL1) were increased in hyperplastic valves of Tgfb2(-/-) embryos, indicating increased expansion and diversification of cushion mesenchyme into the cartilage cell lineage during heart development. Finally, Western blot and immunohistochemistry analyses indicate that the activation of SMAD2/3 was decreased in Tgfb2(-/-) embryos during valve remodeling. Collectively, the data indicate that TGFβ2 promotes valve remodeling and differentiation by inducing matrix organization and suppressing cushion mesenchyme differentiation into cartilage cell lineage during heart development.
authors.affiliation: BIO5 Institute, University of Arizona, Tucson, Arizona; Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona, USA. azharm@email.arizona.edu
authors.forename: Mohamad
authors.initials: M
authors.lastname: Azhar
authors.forename: Kristen
authors.initials: K
authors.lastname: Brown
authors.forename: Connie
authors.initials: C
authors.lastname: Gard
authors.forename: Hwudaurw
authors.initials: H
authors.lastname: Chen
authors.forename: Sudarsan
authors.initials: S
authors.lastname: Rajan
authors.forename: David A
authors.initials: DA
authors.lastname: Elliott
authors.forename: Mark V
authors.initials: MV
authors.lastname: Stevens
authors.forename: Todd D
authors.initials: TD
authors.lastname: Camenisch
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Conway
authors.forename: Thomas
authors.initials: T
authors.lastname: Doetschman
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D006321:Heart / Q000196:embryology*; D006351:Heart Valves / Q000196:embryology / Q000378:metabolism*; D007150:Immunohistochemistry; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; D053781:Transforming Growth Factor beta2