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Nogo-B receptor modulates angiogenesis response of pulmonary artery endothelial cells through eNOS coupling. Am J Respir Cell Mol Biol 2014 Aug;51(2):169-77

Date

02/27/2014

Pubmed ID

24568601

Pubmed Central ID

PMC4148038

DOI

10.1165/rcmb.2013-0298OC

Abstract

Nogo-B, a reticulon-4 isoform, modulates the motility and adhesion of vascular endothelial cells after binding to its receptor, Nogo-B receptor (NgBR). Nogo-B/NgBR pathway contributes to vascular remodeling and angiogenesis, but the role of this pathway in the angiogenesis of developing lungs remains unknown. We previously reported that angiogenesis function of pulmonary artery endothelial cells (PAECs) is impaired by increased reactive oxygen species formation in a fetal lamb model of intrauterine pulmonary hypertension (IPH). Here, we report that Nogo-B/NgBR pathway is altered in IPH, and that decreased NgBR expression contributes to impaired angiogenesis in IPH. We observed a decrease in NgBR levels in lysates of whole lung or PAECs from fetal lambs with IPH compared with controls. Overexpression of NgBR in IPH PAECs rescued the in vitro angiogenesis defects and increased the phosphorylation of both Akt and endothelial nitric oxide synthase at serine(1179) as well as the levels of both manganese superoxide dismutase and GTP cyclohydrolase-1. Consistent with the phenotype of IPH PAECs, knockdown of NgBR in control PAECs decreased the levels of nitric oxide, increased the levels of reactive oxygen species, and impaired in vitro angiogenesis. Our data demonstrate that NgBR mediates PAEC angiogenesis response through the modulation of Akt/endothelial nitric oxide synthase functions, and its decreased expression is mechanistically linked to IPH-related angiogenesis defects in the developing lungs.

Author List

Teng RJ, Rana U, Afolayan AJ, Zhao B, Miao QR, Konduri GG

Authors

Adeleye James Afolayan MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin
Girija Ganesh Konduri MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
Ru-Jeng Teng MD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cells, Cultured
Disease Models, Animal
Endothelial Cells
GTP Cyclohydrolase
Myelin Proteins
Neovascularization, Physiologic
Nitric Oxide
Nitric Oxide Synthase Type III
Nogo Proteins
Persistent Fetal Circulation Syndrome
Phosphorylation
Proto-Oncogene Proteins c-akt
Pulmonary Artery
RNA Interference
Reactive Oxygen Species
Receptors, Cell Surface
Sheep
Signal Transduction
Superoxide Dismutase
Transfection
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc