δEF1 mediates TGF-β signaling in vascular smooth muscle cell differentiation

Alteration in the differentiated state of smooth muscle cells (SMCs) is known to be integral to vascular development and the pathogenesis of vascular disease. However, it is still largely unknown how environmental cues translate into transcriptional control of SMC genes. We found that delta EF1 is upregulated during SMC differentiation and selectively transactivates the promoters of SMC differentiation marker genes, SM alpha-actin and SM myosin heavy chain (SM-MHC). delta EF1 physically interacts with SRF and Smad3, resulting in a synergistic activation of SM a-actin promoter. Chromatin immunoprecipitation assays and knockdown experiments showed that delta EF1 is involved in the control of the SMC differentiation programs induced by TGF-beta signaling. Overexpression of delta EF1 inhibited neointima formation and promoted SMC differentiation, whereas heterozygous dEF1 knockout mice exhibited exaggerated neointima formation. It thus appears delta EF1 mediates SMC differentiation via interaction with SRF and Smad3 during development and in vascular disease.