Olfactomedin 2, a novel regulator for transforming growth factor‐β‐induced smooth muscle differentiation (866.1)

Abstract

Olfactomedin 2 (Olfm2) is a developmentally regulated gene and mediates the early nervous system development. The role of Olfm2 in smooth muscle cell (SMC) differentiation, however, remains elusive. In this study, we found that Olfm2 was induced in TGF‐β‐stimulated SMC differentiation of human embryonic mesenchymal cells. Olfm2 knockdown suppressed TGF‐β‐induced expression of SMC markers including smooth muscle α‐actin (α‐SMA), SM22α and smooth muscle myosin heavy chain (SMMHC). Olfm2 overexpression, on the other hand, promoted SMC marker expression. TGF‐β induced Olfm2 nuclear accumulation, indicating that Olfm2 may function as a nuclear factor and be involved in transcriptional activation of SMC marker genes. Indeed, Olfm2 regulated SMC marker promoter activity in a serum response factor (SRF)‐CArG dependent manner. Mechanistically, Olfm2 physically and functionally interacted with SRF, but did not alter its binding affinity to CArG elements. Instead, Olfm2 facilitated the interaction between myocardin and SRF, which is required for SMC marker gene transcription. Taken together, our data demonstrate that Olfm2 is a novel regulator for SMC differentiation and regulates SMC differentiation through enhancing the interaction of myocardin with SRF.