The basic helix-loop-helix transcription factor scleraxis regulates fibroblast collagen synthesis

Leon Espira, Lise Lamoureux, Stephen C. Jones, Robert D. Gerard, Ian M C Dixon, Michael P. Czubryt

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

The transcription factor scleraxis has been implicated in regulating the development of collagen-rich tissues such as tendons and cardiac valves, but its role in general collagen synthesis in the heart is unknown. Scleraxis expression in cardiac fibroblasts was examined, and its ability to regulate gene expression of collagen Iα2, the predominant cardiac collagen isoform, was assayed. Using real-time PCR, we demonstrate here that scleraxis mRNA is up-regulated by the profibrotic agonist TGF-β1 in rat cardiac myofibroblasts, and that phenoconversion of fibroblasts to myofibroblasts similarly increases scleraxis expression. Over-expression of scleraxis in NIH-3T3 or primary rat cardiac fibroblasts by adenoviral gene delivery is sufficient to significantly increase collagen Iα2 gene expression. Using luciferase reporter assays, we demonstrate that scleraxis transactivates the human collagen Iα2 promoter in a DNA- and protein-binding dependent manner. Intriguingly, examination of infarcted rat hearts reveals a nearly four-fold increase in scleraxis expression in the infarct scar, but not in non-infarcted tissue. These data support a novel and previously unknown role for scleraxis in the regulation of collagen gene expression in the heart, including in post-infarct scar formation.

Original languageEnglish (US)
Pages (from-to)188-195
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume47
Issue number2
DOIs
StatePublished - Aug 1 2009

Keywords

  • Cardiac fibroblasts
  • Cardiac myofibroblasts
  • Extracellular matrix
  • Fibrosis
  • Gene expression

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'The basic helix-loop-helix transcription factor scleraxis regulates fibroblast collagen synthesis'. Together they form a unique fingerprint.

Cite this