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: TGF-β is an important determinant for SM lineage. To determine the role of Olfm2 in TGF-β–induced SM differentiation, we examined the expression of Olfm2 and SM markers in TGF-β–treated hES-MCs. As shown in Figure 1, Olfm2 expression markedly increased soon after TGF-β induction, and TGF-β induced Olfm2 expression in a time-dependent manner, with an 8.4-fold increase after 48-h treatment (Figure 1, A and B). Of importance, Olfm2 induction occurred earlier than expression of SM markers α-SMA, SM22α, and SMMHC (Figure 1, A–E, and Supplemental Figure S1). Moreover, Olfm2 expression was observed in smooth muscle of human aorta tissue (Figure 1F). These data suggest that Olfm2 is involved in TGF-β–induced SM differentiation.
Affiliation: Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602.