This study suggests the potential role of HERP1 in the regulation of SMA expression in BM-derived
BMS-907351 in neointima. We observed that only a limited proportion of BM-derived cells express SMA despite extensive expression of Notch3 and Jagged1 throughout the neointima and the adventitia. Reciprocal relationship between SMA and HERP1 expression prompted us to hypothesize that the ability of Notch signaling to induce SMA expression was inhibited by HERP1. Recently, Tang et al. reported that Notch-HRT constitutes a negative feedback loop to control the expression of SMC differentiation markers [13]. They demonstrated that HRT suppresses binding of Notch-ICD/RBP-Jk complex to the SMA promoter, suggesting that a balance between Notch signaling and HRT/HERP activity determines the expression of SMC marker gene expression. Of note,
expression of HRT/HERP is induced by several factors such as transforming growth factor β family and c-Jun and heparin binding epidermal growth factor other than Notch signaling [14], [15] and [16]. Synergistic enhancement of expression of Notch target genes, in combination with other factors, is also well-known [10], [14] and [28]. For example, expression of HERP2 or smooth muscle-myosin heavy chain (SM-MHC) by Notch stimulation is enhanced by BMP or myocardin, respectively [10], [14] and [28]. Taken together, we suggest that after vascular injury, not only Notch signaling but also various growth factors activate HERP1 expression, which consequently attenuate or even nullify Notch-dependent transcriptional activation of the SMA gene expression.
