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1-Adrenergic stimulation
of FGF-2 promoter in cardiac myocytes and in adult transgenic mouse
hearts
1 Department of Physiology and 2 Department of Human Anatomy and Cell Sciences, Institute of Cardiovascular Science, St. Boniface Hospital Research Center, University of Manitoba, Winnipeg, Manitoba, Canada R3E 3J7
Fibroblast growth factor (FGF-2), a
mitogenic, angiogenic, and cardioprotective agent, is reported to be
released from the postnatal heart by a mechanism of transient
remodeling of the sarcolemma during contraction. This release can be
increased with adrenergic stimulation. RNA blotting was used to assess
whether FGF-2 synthesis in neonatal rat cardiomyocytes might also be
regulated by adrenergic stimulation. FGF-2 RNA levels were increased
after treatment with norepinephrine for 6 h or with the 
-adrenergic agonist phenylephrine for 48 h. To assess an effect on transcription, neonatal rat cardiomyocytes were transfected with a hybrid rat FGF-2
promoter/luciferase gene
(
1058FGFp.luc) and treated
with norepinephrine or phenylephrine for 6 or 48 h, respectively. FGF-2 promoter activity was increased two- to sevenfold in an
1-specific manner. Putative
phenylephrine-responsive elements (PEREs) were identified at positions
780 and 761 relative to a major transcription initiation
site. However, deletion analysis of
1058FGFp.luc showed that the
phenylephrine response was independent of the putative PEREs, cell
contraction, and Ca2+ influx. In
transgenic mice expressing
1058FGFp.luc, a significant three- to sevenfold stimulation of FGF-2 promoter activity was detected
in the hearts of two independent lines 6 h after intraperitoneal administration of phenylephrine (50 mg/kg). This increase was still
apparent at 24 h but was not detected at 48 h posttreatment. Analysis
of FGF-2 mRNA in normal mouse hearts revealed accumulation of the
6.1-kb transcript at 24 h. Control of local FGF-2 synthesis at the
transcriptional level through adrenergic stimulation may be important
in the response to injury as well as in the maintenance of a healthy myocardium.
basic fibroblast growth factor; rat fibroblast growth factor-2 gene; phenylephrine; gene transfer
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