Calcitriol downregulates fibroblast growth factor receptor 1 through histone deacetylase activation in HL-1 atrial myocytes.
J Biomed Sci
; 25(1): 42, 2018 May 18.
Article
em En
| MEDLINE
| ID: mdl-29776409
ABSTRACT
BACKGROUND:
Fibroblast growth factor (FGF)-2 plays a crucial role in the pathophysiology of cardiovascular diseases (CVDs). FGF-2 was reported to induce cardiac hypertrophy through activation of FGF receptor 1 (FGFR1). Multiple laboratory findings indicate that calcitriol may be a potential treatment for CVDs. In this study, we attempted to investigate whether calcitriol regulates FGFR1 expression to modulate the effects of FGF-2 signaling in cardiac myocytes and explored the potential regulatory mechanism.METHODS:
Western blot, polymerase chain reaction, small interfering RNA, fluorometric activity assay, and chromatin immunoprecipitation (ChIP) analyses were used to evaluate FGFR1, FGFR2, FGFR3, FGFR4, phosphorylated extracellular signal-regulated kinase (p-ERK), ß-myosin heavy chain (ß-MHC), phosphorylated phospholipase Cγ (p-PLCγ), nuclear factor of activated T cells (NFAT), and histone deacetylase (HDAC) expressions and enzyme activities in HL-1 atrial myocytes without and with calcitriol (1 and 10 nM) treatment, in the absence and presence of FGF-2 (25 ng/mL) or suberanilohydroxamic acid (SAHA, a pan-HDAC inhibitor, 1 µM).RESULTS:
We found that calcitriol-treated HL-1 cells had significantly reduced FGFR1 expression compared to control cells. In contrast, expressions of FGFR2, FGFR3, and FGFR4 were similar between calcitriol-treated and control HL-1 cells. FGF-2-treated HL-1 cells had similar PLCγ phosphorylation and nuclear/cytoplasmic NFAT expressions compared to control cells. FGF-2 induced lower expressions of p-ERK and ß-MHC in calcitriol-treated HL-1 cells than in control cells. FGFR1-knockdown blocked FGF-2 signaling and reversed the protective effects of calcitriol. Compared to control cells, calcitriol-treated HL-1 cells had higher nuclear HDAC activity. The ChIP analysis demonstrated a significant decrease in acetyl-histone H4, which is associated with an increase in HDAC3 in the FGFR1 promoter. Calcitriol-mediated FGFR1 downregulation was attenuated in the presence of SAHA.CONCLUSIONS:
Calcitriol diminished FGFR1 expression through HDAC activation, which ameliorated the harmful effects of FGF-2 on cardiac myocytes.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vitaminas
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Calcitriol
/
Transdução de Sinais
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Miócitos Cardíacos
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Receptor Tipo 1 de Fator de Crescimento de Fibroblastos
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Histona Desacetilase 1
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article