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The function of cAMP responsive element modulator (CREM) in PDGF induced proliferation of vascular smooth muscle cells
Author(s) -
Seidl Matthias Dodo,
Hildebrandt Iris,
Klugstedt Christian,
Nunes Frank,
Endo Shogo,
Kojima Nobuhiko,
Schmitz Wilhelm,
Müller Frank Ulrich
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1139.1
Subject(s) - platelet derived growth factor receptor , vascular smooth muscle , forskolin , platelet derived growth factor , medicine , growth factor , biology , endocrinology , neointima , gene isoform , pdgfra , microbiology and biotechnology , cell growth , receptor , cancer research , gene , biochemistry , restenosis , gist , stromal cell , stimulation , smooth muscle , stent
The transcription factor CREM plays an important role in cAMP mediated gene expression. Here we want to clarify the role of CREM in vasculature particularly with regard to the regulation of VSMCs proliferation, using CREM (CKO) and CREM isoform ICER (IKO) deficient mice. CKO mice showed an increase of neointima formation associated with a higher proliferation rate of aortic VSMCs under platelet‐derived growth factor (PDGF) treatment. The PDGF alpha receptor (Pdgfra) promoter was inducible by cAMP and mRNA was upregulated in aortae and PDGF‐treated primary VSMCs of CKO mice. In untreated IKO‐VSMCs the proportion of proliferating cells was higher as compared to WT‐VSMCs, while no differences were observed under PDGF treatment. Induction of cAMP by forskolin reduced the proliferation rate of both IKO and WT‐VSMCs under PDGF treatment. Accordingly, ICER was linked to the elevated proliferation of VSMCs under non‐stimulated conditions, however, other CREM isoforms than ICER inhibit PDGF‐mediated proliferation of VSMCs possibly by modulation of cAMP‐dependent Pdgfra gene regulation. (supported by DFG)