Transforming growth factor Beta2 is required for valve remodeling during heart development

Mohamad Azhar, Kristen Brown, Connie Gard, Hwudaurw Chen, Sudarsan Rajan, David A. Elliott, Mark V. Stevens, Todd D. Camenisch, Simon J. Conway, Thomas Doetschman

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2127-2141
Number of pages15
JournalDevelopmental Dynamics
Issue number9
StatePublished - Sep 2011


  • Heart development
  • Transforming growth factor beta
  • Valves

ASJC Scopus subject areas

  • Developmental Biology


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