Repulsive Guidance Molecule a Inhibits Angiogenesis by Downregulating VEGF and Phosphorylated Focal Adhesion Kinase In Vitro

Frontiers in Neurology

Rong Wang¹  Rongrong Zhang²  Gang Zhang²  Qi Li²  Xinyue Qin²  Ke Cheng²  Yu Wang³ 

[1] Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China;Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China;Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China;

关键词: repulsive guidance molecule a;    VEGF;    phosphorylated focal adhesion kinase;    angiogenesis;    neogenin;   

DOI  :  10.3389/fneur.2017.00504

来源: DOAJ

【 摘 要 】

Repulsive guidance molecule a (RGMa) is a major neuron guidance factor in central nervous systems. We previously found that inhibition of RGMa could greatly enhance neural function rehabilitation in rats after MCAO/reperfusion. Neuron guidance factors are often regulators of angiogenesis. However, the effect of RGMa on angiogenesis and its mechanisms remain to be determined. Here, we investigated the effect of RGMa on endothelial cell (EC) proliferation, migration, tube formation, and cytoskeleton reassembly. The addition of recombinant RGMa significantly decreased the proliferation, migration, and tube formation of ECs. It also decreased the level of phosphorylated focal adhesion kinase (p-FAK Tyr397). Furthermore, the F-actin of the cytoskeleton assembly was obviously suppressed, with decreased filopodia and lamellipodia after the addition of RGMa. Knockout of neogenin or Unc5b significantly diminished RGMa’s inhibition of EC migration, tube formation, and cytoskeleton reassembly. RGMa-induced p-FAK (Tyr397) decrease was also abolished by knockout of neogenin or Unc5b. These results indicate that RGMa may be a negative regulator of angiogenesis through downregulating VEGF and p-FAK (Tyr397) via neogenin and Unc5b in vitro.

【 授权许可】

Unknown