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

• Published in: Cardiovascular research Vol. 87; no. 1; pp. 102 - 110
• Main Authors: Sofronescu, Alina G., Detillieux, Karen A., Cattini, Peter A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.2010
• Subjects: Biological and medical sciences; Cardiology. Vascular system; FGF-16; Gene regulation; Isoproterenol; Medical sciences; Mouse and human heart; Nuclear factor-kappaB; Human; Heart; Gene regulation; Rodentia; Mouse and human heart; Stimulation; Activation; Phlebology; FGF-16; Vertebrata; Regulation(control); Mammalia; Postnatal; Gene; Mouse; Isoproterenot; Animal; Adult; Nuclear factor-kappaB; Circulatory system; Transcription factor NFκB; Cardiology; Cell
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/cvq025

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 results Assessments of Fgf-16 promoter activity were made using truncated and transfected hybrid genes with NF-κB inhibitors and/or β-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.