title: Neuromedin B induces angiogenesis via activation of ERK and Akt in endothelial cells.
abstract: Neuromedin B (NMB) is one of the bombesin-like peptides in mammals. Recently, bombesin-like peptides have been characterized as growth factors in highly vascularized tumors. In this study, we report that NMB potently stimulates in vivo neovascularization in a mouse Matrigel plug and the sprouting of endothelial cells ex vivo in rat aortic rings. In addition, NMB increases the migration and tube formation in human umbilical vein endothelial cells (HUVECs). Moreover, treatment of HUVECs with NMB activates the extracellular signal-regulated kinase 1/2 (ERK(1/2)), Akt, and endothelial nitric oxide synthase (eNOS) and increases the level of NO production in a dose- and time-dependent manner. Furthermore, ERK activation and angiogenic sprouting in response to NMB are significantly blocked by the MEK inhibitor. Inhibition of phosphatidylinositol 3-kinase (PI3K) suppresses the NMB-stimulated tubular formation of HUVECs, along with reduction in the phosphorylation of Akt and eNOS. Taken together, these results indicate that NMB is a novel angiogenic peptide, and its angiogenic activity is mediated by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent pathways. This study suggests that NMB may play important roles in mediating a variety of pathophysiological angiogenesis.
authors.affiliation: School of Dentistry, Pusan National University, Yangsan, South Korea.
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Park
authors.forename: Su-Ryun
authors.initials: SR
authors.lastname: Kim
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Bae
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Choi
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Bae
authors.forename: Eok-Cheon
authors.initials: EC
authors.lastname: Kim
authors.forename: Woo Jean
authors.initials: WJ
authors.lastname: Kim
authors.forename: Hye-Ock
authors.initials: HO
authors.lastname: Jang
authors.forename: Il
authors.initials: I
authors.lastname: Yun
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Moon-Kyoung
authors.initials: MK
authors.lastname: Bae
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D015287:Neurokinin B; C038393:neuromedin B; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases