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NFAT‐dependent regulation of Protein C Receptor (PROCR/EPCR) in vascular smooth muscle cell phenotypic modulation
Author(s) -
Lee Monica Y,
Garvey Sean M,
Wamhoff Brian R
Publication year - 2011
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.25.1_supplement.1115.13
Subject(s) - nfat , vascular smooth muscle , biology , microbiology and biotechnology , phenotype , gene , transcription factor , genetics , endocrinology , smooth muscle
Calcineurin (Cn) and the NFAT family of transcription factors are critical in vascular smooth muscle cell (SMC) development and pathology. Here, we use a genomics approach to identify NFAT gene targets activated during PDGF‐BB‐induced SMC phenotypic modulation. Genome‐wide expression arrays were used to identify genes both 1) differentially activated in response to PDGF‐BB, and 2) whose differential expression was reduced by both the Cn inhibitor, cyclosporin A and the NFAT inhibitor, A‐285222. The top 20 pharmacologically sensitive genes were validated by qRT‐PCR analysis of PDGF‐BB‐treated SMCs in the presence of Cn/NFAT inhibitors. In all experiments, protein C receptor (PROCR) gene activation was reduced. The molecular mechanisms governing PROCR expression in vascular cells is currently unknown. The PROCR promoter contains a species‐conserved, NFAT binding site at the −8 position. We show that PROCR expression is virtually absent in untreated, quiescent SMCs. PDGF‐BB stimulation, however, induces significant PROCR promoter activity and downstream protein expression in a Cn/NFAT‐dependent manner. Moreover, basal medial SMC PROCR levels in vivo is barely detectable by immunostaining but induced in the neointima as early as 7 days following acute vascular injury in rat carotid arteries. These data suggest that PROCR induction is implicated in vascular restenosis and consequent inward remodeling.