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Modulation of Pulmonary Vascular Smooth Muscle Cell Phenotype in Hypoxia: Role of Myocardin and ELK‐1
Author(s) -
Zhou Weilin,
Raj J Usha
Publication year - 2008
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.22.1_supplement.1174.11
Subject(s) - myocardin , serum response factor , microbiology and biotechnology , transcription factor , hypoxia (environmental) , biology , chromatin immunoprecipitation , gene expression , vascular smooth muscle , hypoxia inducible factors , phosphorylation , messenger rna , chemistry , gene , endocrinology , promoter , biochemistry , smooth muscle , organic chemistry , oxygen
Hypoxia triggers pulmonary vascular remodeling, which is associated with vascular smooth muscle cell (SMC) phenotype modulation from a contractile to a synthetic state. Altered expression of cGMP‐dependent protein kinase (PKG) after hypoxia is implicated in SMC phenotype modulation. But the mechanism of SMC phenotype modulation after hypoxia at a gene transcriptional level is not clear. In this study, we found that in pulmonary vascular SMC, hypoxia (24h) significantly down‐regulated protein and mRNA expression of Myocardin, but up‐regulated mRNA expression of E‐26‐like protein 1 (Elk‐1). Acute hypoxia (1h) also induced phosphorylation of ELK‐1. Data from chromatin immunoprecipitation assay showed that under hypoxia conditions, less Myocardin and more ELK‐1 was bound to serum response factor (SRF), the transcription factor that is involved in SMC specific gene transcription. These data indicate that hypoxia activates ELK‐1 and inactivates Myocardin, thus inhibiting SRF function, suppressing SMC specific gene transcription and promoting SMC modulation to a de‐differentiated, synthetic state. Inhibition of PKG by PKG siRNA down‐regulated the expression of Myocardin, but up‐regulated the expression of ELK‐1, indicating that PKG may modulate SMC phenotype via regulation of Myocardin and ELK‐1.