cAMP-response element-binding protein mediates prostaglandin F -induced hypertrophy of vascular smooth muscle cells

Kae Fukuyama, Toshihiro Ichiki, Hiroki Ono, Tomotake Tokunou, Naoko Iino, Satoko Masuda, Hideki Ohtsubo, Akira Takeshita

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16 Citations (Scopus)

Abstract

Prostaglandin F (PGF) is a vasoactive factor that causes constriction and hypertrophy of vascular smooth muscle cells (VSMCs). However, the mechanism of PGF-induced hypertrophy is largely unknown. Cyclic AMP-response element (CRE)-binding protein (CREB), the best characterized stimulus-induced transcription factor, activates transcription of target genes with CRE and promotes cell growth. We examined the role of CREB in PGF-induced hypertrophy of VSMCs. PGF induced phosphorylation of CREB at serine 133, which is a critical marker of activation, after 5-10 min of stimulation in a dose-dependent manner. Pharmacological inhibition of extracellular signal-regulated protein kinase and p38 mitogen-activated protein kinase (p38-MAPK) suppressed PGF -induced CREB phosphorylation. Inhibition of epidermal growth factor receptor (EGFR) and mitogen- and stress-activated protein kinase-1 also suppressed PGF-induced CREB phosphorylation. Overexpression of dominant-negative form of CREB (AdCREB M1), of which serine 133 was replaced with alanine, inhibited PGF-induced c-fos mRNA expression as well as hypertrophy of VSMCs [hypertrophy index (μg/104 cell); control 8.13, PGF 9.85, AdCREB M1 7.91, and AdCREB M1 + PGF 8.43]. These results suggest that PGF activated CRE-dependent gene transcription through EGFR transactivation, and the CREB pathway plays a critical role in PGF-induced hypertrophy of VSMCs.

Original languageEnglish
Pages (from-to)910-918
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume338
Issue number2
DOIs
Publication statusPublished - Dec 16 2005

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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