Olfactomedin 2, a novel regulator for transforming growth factor-β-induced smooth muscle differentiation of human embryonic stem cell-derived mesenchymal cells.
Bottom Line: Olfm2 also inhibited HERP1 expression.Moreover, blockade of Olfm2 expression inhibited TGF-β-induced SRF binding to SM gene promoters in a chromatin setting, whereas overexpression of Olfm2 dose dependently enhanced SRF binding.These results demonstrate that Olfm2 mediates TGF-β-induced SM gene transcription by empowering SRF binding to CArG box in SM gene promoters.
Affiliation: Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602.Show MeSH
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Mentions: Myocardin (Myocd) is a transcriptional coactivator of SRF, and Myocd-SRF interaction is crucial for the differentiation of SM lineage (Wang et al., 2001, 2002). Therefore we tested whether Olfm2 affects SRF and Myocd expression as well as their interaction. We found that the ectopic expression of Olfm2 had no effect on mRNA expression of either SRF or Myocd (Figure 6, A–C). To determine whether Olfm2 affects the interaction between SRF and Myocd, we transfected hES-MCs with FLAG-tagged Myocd expression plasmid and performed CoIP assays with endogenous SRF. As shown in Figure 6, D and E, Olfm2 did not alter the interaction between SRF and Myocd. These data suggest that mechanisms other than modulation of SRF/Myocd binding are involved in Olfm2-mediated SM differentiation.
Affiliation: Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602.