Expression of placenta growth factor is regulated by both VEGF and hyperglycaemia via VEGFR-2

Bojun Zhao, Jun Cai, Mike Boulton

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Placenta growth factor (PlGF) has been implicated in both physiological and pathological angiogenesis; however, little is known about what regulates its expression. In this study, retinal microvascular endothelial cells and pericytes were exposed to varying concentrations of VEGF and glucose and PlGF expression measured by RT-PCR and Western blotting. Both PlGF mRNA and protein were observed in unstimulated microvascular endothelial cells with only weak expression in pericytes. In endothelial cells, VEGF (100 ng/ml) and glucose (15 mM) induced an increase in expression of PlGF at both the mRNA and protein level while no effect was observed for pericytes. The increase in PlGF expression could be totally abolished by blocking VEGFR-2, and in the case of glucose by neutralising VEGF. VEGF-stimulated PlGF expression was largely inhibited by PD 98059, an inhibitor of mitogen-activated protein kinase (MAPK) and partially by GF 109203X, an inhibitor of protein kinase C (PKC), indicating that VEGF up-regulates PlGF expression via the MAPK signalling pathway and partially through PKC. Taken together, our findings suggest that VEGF orchestrates the contribution of PlGF in angiogenesis via more than one intracellular pathway and that hyperglycaemia, as occurs in diabetes, is an important regulator of PlGF expression via VEGF up-regulation.

Original languageEnglish (US)
Pages (from-to)239-246
Number of pages8
JournalMicrovascular Research
Volume68
Issue number3
DOIs
StatePublished - Nov 2004
Externally publishedYes

Fingerprint

Vascular Endothelial Growth Factor Receptor-2
Hyperglycemia
Vascular Endothelial Growth Factor A
Intercellular Signaling Peptides and Proteins
Pericytes
Endothelial cells
Endothelial Cells
Mitogen-Activated Protein Kinases
Glucose
Protein Kinase C
Up-Regulation
Physiologic Neovascularization
Pathologic Neovascularization
Placenta Growth Factor
Messenger RNA
Medical problems
Proteins
Western Blotting
Polymerase Chain Reaction

Keywords

  • Angiogenesis
  • Endothelial cells
  • Hyperglycaemia
  • Pericytes
  • Placenta growth factor
  • Proliferative diabetic retinopathy
  • Vascular endothelial growth factor
  • Vascular endothelial growth factor receptor 2

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine

Cite this

Expression of placenta growth factor is regulated by both VEGF and hyperglycaemia via VEGFR-2. / Zhao, Bojun; Cai, Jun; Boulton, Mike.

In: Microvascular Research, Vol. 68, No. 3, 11.2004, p. 239-246.

Research output: Contribution to journalArticle

Zhao, Bojun ; Cai, Jun ; Boulton, Mike. / Expression of placenta growth factor is regulated by both VEGF and hyperglycaemia via VEGFR-2. In: Microvascular Research. 2004 ; Vol. 68, No. 3. pp. 239-246.
@article{772ef2c0cc714783aa2ab868c4d655a8,
title = "Expression of placenta growth factor is regulated by both VEGF and hyperglycaemia via VEGFR-2",
abstract = "Placenta growth factor (PlGF) has been implicated in both physiological and pathological angiogenesis; however, little is known about what regulates its expression. In this study, retinal microvascular endothelial cells and pericytes were exposed to varying concentrations of VEGF and glucose and PlGF expression measured by RT-PCR and Western blotting. Both PlGF mRNA and protein were observed in unstimulated microvascular endothelial cells with only weak expression in pericytes. In endothelial cells, VEGF (100 ng/ml) and glucose (15 mM) induced an increase in expression of PlGF at both the mRNA and protein level while no effect was observed for pericytes. The increase in PlGF expression could be totally abolished by blocking VEGFR-2, and in the case of glucose by neutralising VEGF. VEGF-stimulated PlGF expression was largely inhibited by PD 98059, an inhibitor of mitogen-activated protein kinase (MAPK) and partially by GF 109203X, an inhibitor of protein kinase C (PKC), indicating that VEGF up-regulates PlGF expression via the MAPK signalling pathway and partially through PKC. Taken together, our findings suggest that VEGF orchestrates the contribution of PlGF in angiogenesis via more than one intracellular pathway and that hyperglycaemia, as occurs in diabetes, is an important regulator of PlGF expression via VEGF up-regulation.",
keywords = "Angiogenesis, Endothelial cells, Hyperglycaemia, Pericytes, Placenta growth factor, Proliferative diabetic retinopathy, Vascular endothelial growth factor, Vascular endothelial growth factor receptor 2",
author = "Bojun Zhao and Jun Cai and Mike Boulton",
year = "2004",
month = "11",
doi = "10.1016/j.mvr.2004.07.004",
language = "English (US)",
volume = "68",
pages = "239--246",
journal = "Microvascular Research",
issn = "0026-2862",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Expression of placenta growth factor is regulated by both VEGF and hyperglycaemia via VEGFR-2

AU - Zhao, Bojun

AU - Cai, Jun

AU - Boulton, Mike

PY - 2004/11

Y1 - 2004/11

N2 - Placenta growth factor (PlGF) has been implicated in both physiological and pathological angiogenesis; however, little is known about what regulates its expression. In this study, retinal microvascular endothelial cells and pericytes were exposed to varying concentrations of VEGF and glucose and PlGF expression measured by RT-PCR and Western blotting. Both PlGF mRNA and protein were observed in unstimulated microvascular endothelial cells with only weak expression in pericytes. In endothelial cells, VEGF (100 ng/ml) and glucose (15 mM) induced an increase in expression of PlGF at both the mRNA and protein level while no effect was observed for pericytes. The increase in PlGF expression could be totally abolished by blocking VEGFR-2, and in the case of glucose by neutralising VEGF. VEGF-stimulated PlGF expression was largely inhibited by PD 98059, an inhibitor of mitogen-activated protein kinase (MAPK) and partially by GF 109203X, an inhibitor of protein kinase C (PKC), indicating that VEGF up-regulates PlGF expression via the MAPK signalling pathway and partially through PKC. Taken together, our findings suggest that VEGF orchestrates the contribution of PlGF in angiogenesis via more than one intracellular pathway and that hyperglycaemia, as occurs in diabetes, is an important regulator of PlGF expression via VEGF up-regulation.

AB - Placenta growth factor (PlGF) has been implicated in both physiological and pathological angiogenesis; however, little is known about what regulates its expression. In this study, retinal microvascular endothelial cells and pericytes were exposed to varying concentrations of VEGF and glucose and PlGF expression measured by RT-PCR and Western blotting. Both PlGF mRNA and protein were observed in unstimulated microvascular endothelial cells with only weak expression in pericytes. In endothelial cells, VEGF (100 ng/ml) and glucose (15 mM) induced an increase in expression of PlGF at both the mRNA and protein level while no effect was observed for pericytes. The increase in PlGF expression could be totally abolished by blocking VEGFR-2, and in the case of glucose by neutralising VEGF. VEGF-stimulated PlGF expression was largely inhibited by PD 98059, an inhibitor of mitogen-activated protein kinase (MAPK) and partially by GF 109203X, an inhibitor of protein kinase C (PKC), indicating that VEGF up-regulates PlGF expression via the MAPK signalling pathway and partially through PKC. Taken together, our findings suggest that VEGF orchestrates the contribution of PlGF in angiogenesis via more than one intracellular pathway and that hyperglycaemia, as occurs in diabetes, is an important regulator of PlGF expression via VEGF up-regulation.

KW - Angiogenesis

KW - Endothelial cells

KW - Hyperglycaemia

KW - Pericytes

KW - Placenta growth factor

KW - Proliferative diabetic retinopathy

KW - Vascular endothelial growth factor

KW - Vascular endothelial growth factor receptor 2

UR - http://www.scopus.com/inward/record.url?scp=13844274499&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13844274499&partnerID=8YFLogxK

U2 - 10.1016/j.mvr.2004.07.004

DO - 10.1016/j.mvr.2004.07.004

M3 - Article

VL - 68

SP - 239

EP - 246

JO - Microvascular Research

JF - Microvascular Research

SN - 0026-2862

IS - 3

ER -