Reactive Oxygen Species in Vascular Formation and Development

Figure 4

Regulation of SMC differentiation by Nox4-derived ROS. Activated Nox4 by TGF-β via its receptor and/or upregulated Nox4 by Nrf3 and/or Pla2g7 leads to up-regulation and phosphorylation of SRF through ROS. The phosphorylated SRF in the nucleus bind to the CArG recruiting myocardin to the promoter of SMC-specific genes. Meanwhile, Nox4-derived ROS can also activate SMC gene expression via p38MAPK pathway. During differentiation, Nox translocates into nucleus. Moreover, Nrf3 and Pla2g7 promote the recruitment of myocardin/SRF complex to CArG box in the promoter region of SMC genes. Importantly, Nrf3 has been shown to bind directly to the unknown Nrf3 binding element within promoter regions of SMC genes.