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.

journal_name

Exp Cell Res

authors

Park HJ,Kim SR,Bae SK,Choi YK,Bae YH,Kim EC,Kim WJ,Jang HO,Yun I,Kim YM,Bae MK

doi

10.1016/j.yexcr.2009.08.009

subject

Has Abstract

pub_date

2009-11-15 00:00:00

pages

3359-69

issue

19

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(09)00366-8

journal_volume

315

pub_type

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