Olfactomedin 2 (Olfm2) is a novel regulator for vascular smooth muscle cell (SMC) differentiation, but it is unclear whether Olfm2 is also involved in SMC phenotypic modulation, an important process associated with vascular injury. In this study, we found that Olfm2 was induced during PDGF-BB-induced SMC phenotypic modulation. Olfm2 knockdown attenuated PDGF-BB-induced suppression of SM marker genes including SM myosin heavy chain and SM22α, and also inhibited PDGF-BB-stimulated SMC proliferation and migration. On the other hand, Olfm2 overexpression down-regulated SM markers gene expression, and promoted SMC proliferation marker PCNA expression. Moreover, PDGF-BB slightly induced expression of Runx2, which interfered with the formation of SRF/myocardin ternary complex, but dramatically enhanced SRF-Runx2 interaction, suggesting that certain factors mediate SRF-Runx2 interaction. Indeed, Olfm2 physically interacted with both SRF and Runx2. Blockade of Olfm2 inhibited SRF association with Runx2, leading to increased association between SRF and myocardin, which in turn activated the transcription of SM markers, whereas overexpression of Olfm2 promoted SRF binding to Runx2. These results demonstrated that Olfm2 mediates the interaction between SRF and Runx2, contributing to SMC phenotypic modulation.
Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single-cell analysis
