FGF-16 is a Target for Adrenergic Stimulation Through NF-kappaB Activation in Postnatal Cardiac Cells and Adult Mouse Heart

Overview

Journal Cardiovasc Res

Specialty Cardiology & Vascular Diseases

Date 2010 Jan 26

PMID 20097674

Citations 6

Authors

Alina G Sofronescu

Karen A Detillieux

Peter A Cattini

Affiliations

Soon will be listed here.

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-kappaB) elements, suggesting that Fgf-16 is regulated via NF-kappaB activation and thereby implicated in a number of cardiac events. Thus, the Fgf-16 gene was investigated as a target for NF-kappaB activation in cardiac cells.

Methods And Results: Assessments of Fgf-16 promoter activity were made using truncated and transfected hybrid genes with NF-kappaB inhibitors and/or beta-adrenergic stimulation via isoproterenol (IsP) treatment (a known NF-kappaB 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-kappaB inhibitor pretreatment. Deletion analysis revealed IsP responsiveness linked to sequences between TATA2 and TATA1 and, more specifically, a NF-kappaB element upstream and adjacent to TATA1 that associates with NF-kappaB p50/p65 subunits in chromatin. Finally, TATA1 and the proximal NF-kappaB element are conserved in the human genome and responsive to IsP.

Conclusion: The mouse and human Fgf-16 gene is a target for NF-kappaB activation in the postnatal heart.

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