FGF-16 is a target for adrenergic stimulation through NF-B activation in postnatal cardiac cells and adult mouse heart

Alina G. Sofronescu, Karen A. Detillieux, Peter A. Cattini

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Aims The fibroblast growth factor (FGF) family plays an important role in cardiac growth and development. However, only FGF-16 RNA levels are reported to increase during the perinatal period and to be expressed preferentially in the myocardium, suggesting control at the transcriptional level and a role for FGF-16 in the postnatal heart. Beyond the identification of two TATA-like elements (TATA1 and TATA2) in the mouse FGF-16 promoter region and the preferential cardiac activity of TATA2, there is no report of Fgf-16 gene regulation. Assessment of promoter sequences, however, reveals putative nuclear factor-kappaB (NF-κB) elements, suggesting that Fgf-16 is regulated via NF-κB activation and thereby implicated in a number of cardiac events. Thus, the Fgf-16 gene was investigated as a target for NF-κB activation in cardiac cells. Methods and resultsAssessments of Fgf-16 promoter activity were made using truncated and transfected hybrid genes with NF-κB inhibitors and/or-adrenergic stimulation via isoproterenol (IsP) treatment (a known NF-κB activator) in culture, and on endogenous mouse and human Fgf-16 genes in situ. The mouse Fgf-16 promoter region was stimulated in response to IsP treatment, but this response was lost with NF-κB inhibitor pretreatment. Deletion analysis revealed IsP responsiveness linked to sequences between TATA2 and TATA1 and, more specifically, a NF-κB element upstream and adjacent to TATA1 that associates with NF-κB p50/p65 subunits in chromatin. Finally, TATA1 and the proximal NF-κB element are conserved in the human genome and responsive to IsP. Conclusion The mouse and human Fgf-16 gene is a target for NF-κB activation in the postnatal heart.

Original languageEnglish (US)
Pages (from-to)102-110
Number of pages9
JournalCardiovascular research
Volume87
Issue number1
DOIs
StatePublished - Jul 1 2010

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Keywords

  • FGF-16
  • Gene regulation
  • Isoproterenol
  • Mouse and human heart
  • Nuclear factor-kappaB

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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