Abstract 16659: Nogo-B Receptor is Required for the Recruitment of Vascular Smooth Muscle Cells to Developing Blood Vessels

Abstract

The blood vessel maturation involves the coordination of two cell types - endothelial cells (EC) and vascular smooth muscle cells (VSMC). Hence, understanding of EC and VSMC migration is an essential step in developing new therapeutic approaches for diseases-associated with blood vessel maturation defects. PDGF plays a critical role in blood vessel maturation by promoting VSMC proliferation and migration via Ras signaling pathway. Although Nogo-B receptor (NgBR) was identified as a cell surface receptor special for the ligand Nogo-B, it acts as a scaffold protein requested for Ras translocation to the plasma membrane, which is a critical step for Ras activation by PDGF receptor and other receptor tyrosine kinases. NgBR is expressed in both EC and VSMC. Previous reports demonstrated the genetic deletion of NgBR in endothelial cells causes the embryonic lethality due to cerebrovascular defects in mice. Here, we further elucidate the roles of NgBR in regulating the recruitment of VSMC in the developing blood vessels. The genetic deletion of NgBR in VSMC also results in embryonic lethality due to impaired VSMC coverage on blood vessels and hemorrhage. Mechanistically, our data demonstrated that NgBR is required for PDGF-induced Ras signaling pathway and VSMC migration. Interestingly, we also appreciate the defects of VSMC recruitment in the blood vessels of NgBR EC-specific knockout mice. Gene profile analysis reveals that NgBR knockdown decreased the expression of PDGF in EC. Collectively, these data demonstrate that NgBR is an integral part of blood vessel maturation process by facilitating VSMC recruitment. Our results suggest that NgBR may be one of the essential genes coordinating the blood vessel development.