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CaMKII‐dependent regulation of HDAC4/5 and gene transcription in vascular smooth muscle cells
Author(s) -
Ginnan Roman Gregory,
Sun Li Yan,
Singer Harold A
Publication year - 2009
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.23.1_supplement.300.3
Subject(s) - microbiology and biotechnology , phenotype , hdac4 , phosphorylation , biology , vascular smooth muscle , transcription factor , mef2 , gene expression , phenotypic switching , repressor , transcription (linguistics) , myocardin , platelet derived growth factor receptor , signal transduction , gene , serum response factor , receptor , genetics , endocrinology , growth factor , linguistics , histone methyltransferase , philosophy , enhancer , smooth muscle
Vascular smooth muscle is well known for phenotype plasticity and upon injury or in response to disease it modulates from a contractile phenotype to a sythetic phenotype that contributes to vascular remodeling. We have demonstrated that increased expression of CaMKII is associated with modulation of VSM to the synthetic phenotype but there is very little direct evidence indicating a function for the kinase in regulating VSM cell gene transcription. Herein, we report that the transcriptional co‐repressors HDAC4/5 are phosphorylated in a CaMKII‐dependent manner . Furthermore, effective suppression of CaMKII expression resulted in decreased HDAC5 phosphorylation in response to PDGF and AngII. Nur77 is an immediate response gene shown to be regulated in a Mef2/HDAC‐dependent manner. Our initial studies in cultured VSM indicate robust activation of nur77 in response to PDGF. Inhibition or suppression of CaMKII resulted in the decrease of Nur77 expression. Taken together, these results lead us to hypothesize that Ca2+ signaling, via CaMKII, regulates VSM gene transcription and may be a determinant of VSM phenotype.