Neuromedin B induces angiogenesis via activation of ERK and Akt in endothelial cells.
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.
Park
Hyun-Joo
HJ
School of Dentistry, Pusan National University, Yangsan, South Korea.
Kim
Su-Ryun
SR
Bae
Soo-Kyung
SK
Choi
Yoon Kyung
YK
Bae
Yun-Hee
YH
Kim
Eok-Cheon
EC
Kim
Woo Jean
WJ
Jang
Hye-Ock
HO
Yun
Il
I
Kim
Young-Myeong
YM
Bae
Moon-Kyoung
MK
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
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