Abstract
p43 is a cofactor of aminoacyl-tRNA synthetase in mammals that effectively inhibits angiogenesis. However, the role of p43 in angiogenesis remains unclear. In the present study, we examined the effects of p43 on angiogenesis using human microvascular endothelial cells-1 (HMEC-1) cells as a model. Our microarray data showed that p43 regulated a number of cytokines, and the majoity of these are involved in the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway. IP-10 was previously shown to inhibit angiogenesis and suppress tumor growth via the JAK-STAT signaling pathway in vitro and in vivo. Our results showed that p43 induces both the mRNA and protein expression of IP-10. Furthermore, we demonstrated that p43 exerted an effect on the JAK-STAT signaling pathway by regulating key factors of the pathway. Using a JAK inhibitor, AG490, we studied the effect of p43 on HMEC-1 cells by blocking the JAK-STAT pathway. We found that AG490 inhibited the induction of IP-10 expression by p43, and suppressed the inhibitory effect of p43 on tubule formation and cell migration in HMEC-1 cells. We concluded that p43 inhibits tubule formation and cell migration by inducing IP-10 through the JAK-STAT signaling pathway, and blocking the JAK-STAT pathway with AG490 diminishes the inhibitory effects of p43 on angiogenesis.