title: p43 induces IP-10 expression through the JAK-STAT signaling pathway in HMEC-1 cells.
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.
authors: Beijing Institute of Biotechnology, Beijing 100071, P.R. China.
authors: Wei
authors: W
authors: Wang
authors: Beijing Institute of Biotechnology, Beijing 100071, P.R. China.
authors: Junjie
authors: J
authors: Tan
authors: National Institutes for Food and Drug Control, Beijing 100071, P.R. China.
authors: Yuhua
authors: Y
authors: Xing
authors: School of Life Sciences, Anhui University, Hefei, Anhui 230039, P.R. China.
authors: Naipeng
authors: N
authors: Kan
authors: Beijing Institute of Biotechnology, Beijing 100071, P.R. China.
authors: Jingyi
authors: J
authors: Ling
authors: School of Life Sciences, Anhui University, Hefei, Anhui 230039, P.R. China.
authors: Guifu
authors: G
authors: Dong
authors: Beijing Institute of Biotechnology, Beijing 100071, P.R. China.
authors: Gang
authors: G
authors: Liu
authors: Beijing Institute of Biotechnology, Beijing 100071, P.R. China.
authors: Huipeng
authors: H
authors: Chen
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D054357:Chemokine CXCL10 / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D055806:Microvessels / Q000166:cytology*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D010444:Peptide Elongation Factor Tu / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D024101:Mitochondrial Proteins; D050794:STAT1 Transcription Factor; C091648:TUFM protein, human; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D053612:Janus Kinases; D010444:Peptide Elongation Factor Tu