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: To determine whether Olfm2 plays a role in SM differentiation, we tested whether Olfm2 is required for TGF-β–induced SM marker expression. As shown in Figure 2, A–E, knockdown of Olfm2 by an adenoviral vector expressing Olfm2 short hairpin RNA (shRNA; adenovirus [Ad]-shOlfm2) significantly attenuated TGF-β–induced SM marker expression, indicating that Olfm2 is essential for TGF-β–induced SM differentiation. To further determine the role of Olfm2 in SM differentiation, we tested whether Olfm2 alone can induce SM marker expression. As shown in Figure 2, F–J, ectopic expression of Olfm2 in serum-starved hES-MCs induced 3.2-, 2.3-, and 3.6-fold increases in α-SMA, SM22α, and SMMHC expression, respectively. These results demonstrate that Olfm2 can promote SM marker gene expression.
Affiliation: Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602.