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


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.


CONCLUSIONS
The mouse and human Fgf-16 gene is a target for NF-kappaB activation in the postnatal heart.
Sofronescu
Alina G
AG
Department of Physiology, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, MB, Canada R3E 0J9.
Detillieux
Karen A
KA
Cattini
Peter A
PA
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D017124:Conserved Sequence; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014162:Transfection; D055815:Young Adult
D000318:Adrenergic beta-Agonists; C512705:FGF16 protein, human; C484686:Fgf16 protein, mouse; D016328:NF-kappa B; D012333:RNA, Messenger; D005346:Fibroblast Growth Factors; D007545:Isoproterenol