Neuropilin-1 regulates vascular endothelial growth factor-mediated endothelial permeability

Patrice M. Becker, Johannes Waltenberger, Robin Yachechko, Tamara Mirzapoiazova, James S.K. Sham, Chun Geun Lee, Jack A. Elias, Alexander Dmitriyevich Verin

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Neuropilin-1 (Npn-1) is a cell surface receptor that binds vascular endothelial growth factor (VEGF), a potent mediator of endothelial permeability, chemotaxis, and proliferation. In vitro, Npn-1 can complex with VEGF receptor-2 (VEGFR2) to enhance VEGFR2-mediated endothelial cell chemotaxis and proliferation. To determine the role of Npn-1/VEGFR2 complexes in VEGF-induced endothelial barrier dysfunction, endothelial cells were stably transfected with Npn1 or VEGFR2 alone (PAE/Npn and PAE/KDR, respectively), or VEGFR2 and Npn-1 (PAE/KDR/Npn-1). Permeability, estimated by measurement of transendothelial electrical resistance (TER), of PAE/Npn and PAE/KDR cell lines was not altered by VEGF165. In contrast, TER of PAE/KDR/Npn-1 cells decreased in dose-dependent fashion following VEGF165 (10 to 200 ng/mL). Activation of VEGFR2, and 2 downstream signaling intermediates (p38 and ERK1/2 MAPK) involved in VEGF-mediated permeability, also increased in PAE/KDR/Npn-1. Consistent with these data, inhibition of Npn-1, but not VEGFR2, attenuated VEGF165-mediated permeability of human pulmonary artery endothelial cells (HPAE), and VEGF121 (which cannot ligate Npn-1) did not alter TER of HPAE. Npn-1 inhibition also attenuated both VEGF165-mediated pulmonary vascular leak and activation of VEGFR2, p38, and ERK1/2 MAPK, in inducible lung-specific VEGF transgenic mice. These data support a critical role for Npn-1 in regulating endothelial barrier dysfunction in response to VEGF and suggest that activation of distinct receptor complexes may determine specificity of cellular response to VEGF.

Original languageEnglish (US)
Pages (from-to)1257-1265
Number of pages9
JournalCirculation research
Volume96
Issue number12
DOIs
StatePublished - Jun 24 2005

Fingerprint

Neuropilin-1
Vascular Endothelial Growth Factor A
Permeability
Vascular Endothelial Growth Factor Receptor
Endothelial Cells
Electric Impedance
Chemotaxis
Pulmonary Artery
Vascular Endothelial Growth Factor Receptor-2
Lung
Cell Surface Receptors
Transgenic Mice
Blood Vessels

Keywords

  • Acute lung injury
  • Chemotaxis
  • Mitogen-activated protein kinase
  • Transendothelial electrical resistance
  • Vascular endothelial growth factor receptor-2

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Becker, P. M., Waltenberger, J., Yachechko, R., Mirzapoiazova, T., Sham, J. S. K., Lee, C. G., ... Verin, A. D. (2005). Neuropilin-1 regulates vascular endothelial growth factor-mediated endothelial permeability. Circulation research, 96(12), 1257-1265. https://doi.org/10.1161/01.RES.0000171756.13554.49

Neuropilin-1 regulates vascular endothelial growth factor-mediated endothelial permeability. / Becker, Patrice M.; Waltenberger, Johannes; Yachechko, Robin; Mirzapoiazova, Tamara; Sham, James S.K.; Lee, Chun Geun; Elias, Jack A.; Verin, Alexander Dmitriyevich.

In: Circulation research, Vol. 96, No. 12, 24.06.2005, p. 1257-1265.

Research output: Contribution to journalArticle

Becker, PM, Waltenberger, J, Yachechko, R, Mirzapoiazova, T, Sham, JSK, Lee, CG, Elias, JA & Verin, AD 2005, 'Neuropilin-1 regulates vascular endothelial growth factor-mediated endothelial permeability', Circulation research, vol. 96, no. 12, pp. 1257-1265. https://doi.org/10.1161/01.RES.0000171756.13554.49
Becker PM, Waltenberger J, Yachechko R, Mirzapoiazova T, Sham JSK, Lee CG et al. Neuropilin-1 regulates vascular endothelial growth factor-mediated endothelial permeability. Circulation research. 2005 Jun 24;96(12):1257-1265. https://doi.org/10.1161/01.RES.0000171756.13554.49
Becker, Patrice M. ; Waltenberger, Johannes ; Yachechko, Robin ; Mirzapoiazova, Tamara ; Sham, James S.K. ; Lee, Chun Geun ; Elias, Jack A. ; Verin, Alexander Dmitriyevich. / Neuropilin-1 regulates vascular endothelial growth factor-mediated endothelial permeability. In: Circulation research. 2005 ; Vol. 96, No. 12. pp. 1257-1265.
@article{6188d636687e4be78f1005ad09e5d737,
title = "Neuropilin-1 regulates vascular endothelial growth factor-mediated endothelial permeability",
abstract = "Neuropilin-1 (Npn-1) is a cell surface receptor that binds vascular endothelial growth factor (VEGF), a potent mediator of endothelial permeability, chemotaxis, and proliferation. In vitro, Npn-1 can complex with VEGF receptor-2 (VEGFR2) to enhance VEGFR2-mediated endothelial cell chemotaxis and proliferation. To determine the role of Npn-1/VEGFR2 complexes in VEGF-induced endothelial barrier dysfunction, endothelial cells were stably transfected with Npn1 or VEGFR2 alone (PAE/Npn and PAE/KDR, respectively), or VEGFR2 and Npn-1 (PAE/KDR/Npn-1). Permeability, estimated by measurement of transendothelial electrical resistance (TER), of PAE/Npn and PAE/KDR cell lines was not altered by VEGF165. In contrast, TER of PAE/KDR/Npn-1 cells decreased in dose-dependent fashion following VEGF165 (10 to 200 ng/mL). Activation of VEGFR2, and 2 downstream signaling intermediates (p38 and ERK1/2 MAPK) involved in VEGF-mediated permeability, also increased in PAE/KDR/Npn-1. Consistent with these data, inhibition of Npn-1, but not VEGFR2, attenuated VEGF165-mediated permeability of human pulmonary artery endothelial cells (HPAE), and VEGF121 (which cannot ligate Npn-1) did not alter TER of HPAE. Npn-1 inhibition also attenuated both VEGF165-mediated pulmonary vascular leak and activation of VEGFR2, p38, and ERK1/2 MAPK, in inducible lung-specific VEGF transgenic mice. These data support a critical role for Npn-1 in regulating endothelial barrier dysfunction in response to VEGF and suggest that activation of distinct receptor complexes may determine specificity of cellular response to VEGF.",
keywords = "Acute lung injury, Chemotaxis, Mitogen-activated protein kinase, Transendothelial electrical resistance, Vascular endothelial growth factor receptor-2",
author = "Becker, {Patrice M.} and Johannes Waltenberger and Robin Yachechko and Tamara Mirzapoiazova and Sham, {James S.K.} and Lee, {Chun Geun} and Elias, {Jack A.} and Verin, {Alexander Dmitriyevich}",
year = "2005",
month = "6",
day = "24",
doi = "10.1161/01.RES.0000171756.13554.49",
language = "English (US)",
volume = "96",
pages = "1257--1265",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "12",

}

TY - JOUR

T1 - Neuropilin-1 regulates vascular endothelial growth factor-mediated endothelial permeability

AU - Becker, Patrice M.

AU - Waltenberger, Johannes

AU - Yachechko, Robin

AU - Mirzapoiazova, Tamara

AU - Sham, James S.K.

AU - Lee, Chun Geun

AU - Elias, Jack A.

AU - Verin, Alexander Dmitriyevich

PY - 2005/6/24

Y1 - 2005/6/24

N2 - Neuropilin-1 (Npn-1) is a cell surface receptor that binds vascular endothelial growth factor (VEGF), a potent mediator of endothelial permeability, chemotaxis, and proliferation. In vitro, Npn-1 can complex with VEGF receptor-2 (VEGFR2) to enhance VEGFR2-mediated endothelial cell chemotaxis and proliferation. To determine the role of Npn-1/VEGFR2 complexes in VEGF-induced endothelial barrier dysfunction, endothelial cells were stably transfected with Npn1 or VEGFR2 alone (PAE/Npn and PAE/KDR, respectively), or VEGFR2 and Npn-1 (PAE/KDR/Npn-1). Permeability, estimated by measurement of transendothelial electrical resistance (TER), of PAE/Npn and PAE/KDR cell lines was not altered by VEGF165. In contrast, TER of PAE/KDR/Npn-1 cells decreased in dose-dependent fashion following VEGF165 (10 to 200 ng/mL). Activation of VEGFR2, and 2 downstream signaling intermediates (p38 and ERK1/2 MAPK) involved in VEGF-mediated permeability, also increased in PAE/KDR/Npn-1. Consistent with these data, inhibition of Npn-1, but not VEGFR2, attenuated VEGF165-mediated permeability of human pulmonary artery endothelial cells (HPAE), and VEGF121 (which cannot ligate Npn-1) did not alter TER of HPAE. Npn-1 inhibition also attenuated both VEGF165-mediated pulmonary vascular leak and activation of VEGFR2, p38, and ERK1/2 MAPK, in inducible lung-specific VEGF transgenic mice. These data support a critical role for Npn-1 in regulating endothelial barrier dysfunction in response to VEGF and suggest that activation of distinct receptor complexes may determine specificity of cellular response to VEGF.

AB - Neuropilin-1 (Npn-1) is a cell surface receptor that binds vascular endothelial growth factor (VEGF), a potent mediator of endothelial permeability, chemotaxis, and proliferation. In vitro, Npn-1 can complex with VEGF receptor-2 (VEGFR2) to enhance VEGFR2-mediated endothelial cell chemotaxis and proliferation. To determine the role of Npn-1/VEGFR2 complexes in VEGF-induced endothelial barrier dysfunction, endothelial cells were stably transfected with Npn1 or VEGFR2 alone (PAE/Npn and PAE/KDR, respectively), or VEGFR2 and Npn-1 (PAE/KDR/Npn-1). Permeability, estimated by measurement of transendothelial electrical resistance (TER), of PAE/Npn and PAE/KDR cell lines was not altered by VEGF165. In contrast, TER of PAE/KDR/Npn-1 cells decreased in dose-dependent fashion following VEGF165 (10 to 200 ng/mL). Activation of VEGFR2, and 2 downstream signaling intermediates (p38 and ERK1/2 MAPK) involved in VEGF-mediated permeability, also increased in PAE/KDR/Npn-1. Consistent with these data, inhibition of Npn-1, but not VEGFR2, attenuated VEGF165-mediated permeability of human pulmonary artery endothelial cells (HPAE), and VEGF121 (which cannot ligate Npn-1) did not alter TER of HPAE. Npn-1 inhibition also attenuated both VEGF165-mediated pulmonary vascular leak and activation of VEGFR2, p38, and ERK1/2 MAPK, in inducible lung-specific VEGF transgenic mice. These data support a critical role for Npn-1 in regulating endothelial barrier dysfunction in response to VEGF and suggest that activation of distinct receptor complexes may determine specificity of cellular response to VEGF.

KW - Acute lung injury

KW - Chemotaxis

KW - Mitogen-activated protein kinase

KW - Transendothelial electrical resistance

KW - Vascular endothelial growth factor receptor-2

UR - http://www.scopus.com/inward/record.url?scp=21844449129&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21844449129&partnerID=8YFLogxK

U2 - 10.1161/01.RES.0000171756.13554.49

DO - 10.1161/01.RES.0000171756.13554.49

M3 - Article

C2 - 15920019

AN - SCOPUS:21844449129

VL - 96

SP - 1257

EP - 1265

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 12

ER -