RGD Reference Report - The basic helix-loop-helix transcription factor scleraxis regulates fibroblast collagen synthesis. - Rat Genome Database

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

Authors: Espira, L  Lamoureux, L  Jones, SC  Gerard, RD  Dixon, IM  Czubryt, MP 
Citation: Espira L, etal., J Mol Cell Cardiol. 2009 Aug;47(2):188-95. doi: 10.1016/j.yjmcc.2009.03.024. Epub 2009 Apr 10.
RGD ID: 8554531
Pubmed: PMID:19362560   (View Abstract at PubMed)
DOI: DOI:10.1016/j.yjmcc.2009.03.024   (Journal Full-text)

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 I alpha 2, 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-beta(1) 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 I alpha 2 gene expression. Using luciferase reporter assays, we demonstrate that scleraxis transactivates the human collagen I alpha 2 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.




Biological Process

  
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Original Reference(s)
Col1a1Ratcellular response to transforming growth factor beta stimulus involved_inIEP PMID:19362560UniProt 


Genes (Rattus norvegicus)
Col1a1  (collagen type I alpha 1 chain)