Expression of vascular endothelial growth factor isoforms and their receptors Flt-1, KDR, and neuropilin-1 in synovial tissues of rheumatoid arthritis

Mika Ikeda, Yasuhiro Hosoda, Shigemichi Hirose, Yasunori Okada, Eiji Ikeda

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Angiogenesis is an indispensable process in the chronic proliferative synovitis and pannus formation of rheumatoid arthritis (RA). Tiffs study examined the expression of vascular endothelial growth factor (VEGF) isoforms and VEGF receptors, Flt-l, KDR and neuropiiin-1, in RA and osteoarthritis (OA) synovia, and studied the relationship between their expression and the synovial angiogenesis. By RT-PCR analysis, the isoform VEGF121 was constitutively expressed in all the RA (17/17 patients) and OA (8/8 patients) synovia. In contrast, the expression of the isoform VEGF165 was observed in 41% of the RA synovia (7/17 patients), but was undetectable in the OA samples (0/8 patients). The receptor Flt-1 was almost constitutively expressed in RA (15/17 patients) and OA (8/8 patients) synovia, while the expression of KDR was detected in the synovia of six RA patients (6/17 patients; 35%) but none of the OA patients (0/8 patients). The expression of neuropilin-1, an isoform-specific receptor for VEGF165 which enhances the binding of VEGF165 to KDR, was also up-regulated in the same RA synovia that expressed KDR. Furthermore, there was a close correlation between the expression of isoform VEGF165 and that of its receptors KDR and neuropilin-1. Morphometric analysis demonstrated that the vascular density is significantly higher in the RA synovial tissues with expression of VEGF165, KDR, and neuropilin-1 than in those without their expression (p<0.01). In situ hybridization and immunohistochemical studies indicated that the cells expressing VEGF are macrophage-like synovial lining cells and spindle-shaped cells in the sublining cell layer. These results suggest that the selective up-regulation of the isoform VEGF165 and its signalling via KDR and neuropilin-1 play an important role in the synovial angiogenesis which occurs in RA. Copyright (C) 2000 John Wiley and Sons, Ltd.

Original languageEnglish
Pages (from-to)426-433
Number of pages8
JournalJournal of Pathology
Volume191
Issue number4
Publication statusPublished - 2000

Fingerprint

Neuropilin-1
Vascular Endothelial Growth Factor A
Rheumatoid Arthritis
Protein Isoforms
Synovial Fluid
Osteoarthritis
Vascular Endothelial Growth Factor Receptor
Synovitis
In Situ Hybridization
Blood Vessels
Up-Regulation
Macrophages

Keywords

  • Angiogenesis
  • Isoform
  • KDR
  • Neuropilin-1
  • Rheumatoid arthritis
  • VEGF

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Expression of vascular endothelial growth factor isoforms and their receptors Flt-1, KDR, and neuropilin-1 in synovial tissues of rheumatoid arthritis. / Ikeda, Mika; Hosoda, Yasuhiro; Hirose, Shigemichi; Okada, Yasunori; Ikeda, Eiji.

In: Journal of Pathology, Vol. 191, No. 4, 2000, p. 426-433.

Research output: Contribution to journalArticle

Ikeda, Mika ; Hosoda, Yasuhiro ; Hirose, Shigemichi ; Okada, Yasunori ; Ikeda, Eiji. / Expression of vascular endothelial growth factor isoforms and their receptors Flt-1, KDR, and neuropilin-1 in synovial tissues of rheumatoid arthritis. In: Journal of Pathology. 2000 ; Vol. 191, No. 4. pp. 426-433.
@article{0b5e5064d07748a19d9d76cf4bc40b08,
title = "Expression of vascular endothelial growth factor isoforms and their receptors Flt-1, KDR, and neuropilin-1 in synovial tissues of rheumatoid arthritis",
abstract = "Angiogenesis is an indispensable process in the chronic proliferative synovitis and pannus formation of rheumatoid arthritis (RA). Tiffs study examined the expression of vascular endothelial growth factor (VEGF) isoforms and VEGF receptors, Flt-l, KDR and neuropiiin-1, in RA and osteoarthritis (OA) synovia, and studied the relationship between their expression and the synovial angiogenesis. By RT-PCR analysis, the isoform VEGF121 was constitutively expressed in all the RA (17/17 patients) and OA (8/8 patients) synovia. In contrast, the expression of the isoform VEGF165 was observed in 41{\%} of the RA synovia (7/17 patients), but was undetectable in the OA samples (0/8 patients). The receptor Flt-1 was almost constitutively expressed in RA (15/17 patients) and OA (8/8 patients) synovia, while the expression of KDR was detected in the synovia of six RA patients (6/17 patients; 35{\%}) but none of the OA patients (0/8 patients). The expression of neuropilin-1, an isoform-specific receptor for VEGF165 which enhances the binding of VEGF165 to KDR, was also up-regulated in the same RA synovia that expressed KDR. Furthermore, there was a close correlation between the expression of isoform VEGF165 and that of its receptors KDR and neuropilin-1. Morphometric analysis demonstrated that the vascular density is significantly higher in the RA synovial tissues with expression of VEGF165, KDR, and neuropilin-1 than in those without their expression (p<0.01). In situ hybridization and immunohistochemical studies indicated that the cells expressing VEGF are macrophage-like synovial lining cells and spindle-shaped cells in the sublining cell layer. These results suggest that the selective up-regulation of the isoform VEGF165 and its signalling via KDR and neuropilin-1 play an important role in the synovial angiogenesis which occurs in RA. Copyright (C) 2000 John Wiley and Sons, Ltd.",
keywords = "Angiogenesis, Isoform, KDR, Neuropilin-1, Rheumatoid arthritis, VEGF",
author = "Mika Ikeda and Yasuhiro Hosoda and Shigemichi Hirose and Yasunori Okada and Eiji Ikeda",
year = "2000",
language = "English",
volume = "191",
pages = "426--433",
journal = "Journal of Pathology",
issn = "0022-3417",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

TY - JOUR

T1 - Expression of vascular endothelial growth factor isoforms and their receptors Flt-1, KDR, and neuropilin-1 in synovial tissues of rheumatoid arthritis

AU - Ikeda, Mika

AU - Hosoda, Yasuhiro

AU - Hirose, Shigemichi

AU - Okada, Yasunori

AU - Ikeda, Eiji

PY - 2000

Y1 - 2000

N2 - Angiogenesis is an indispensable process in the chronic proliferative synovitis and pannus formation of rheumatoid arthritis (RA). Tiffs study examined the expression of vascular endothelial growth factor (VEGF) isoforms and VEGF receptors, Flt-l, KDR and neuropiiin-1, in RA and osteoarthritis (OA) synovia, and studied the relationship between their expression and the synovial angiogenesis. By RT-PCR analysis, the isoform VEGF121 was constitutively expressed in all the RA (17/17 patients) and OA (8/8 patients) synovia. In contrast, the expression of the isoform VEGF165 was observed in 41% of the RA synovia (7/17 patients), but was undetectable in the OA samples (0/8 patients). The receptor Flt-1 was almost constitutively expressed in RA (15/17 patients) and OA (8/8 patients) synovia, while the expression of KDR was detected in the synovia of six RA patients (6/17 patients; 35%) but none of the OA patients (0/8 patients). The expression of neuropilin-1, an isoform-specific receptor for VEGF165 which enhances the binding of VEGF165 to KDR, was also up-regulated in the same RA synovia that expressed KDR. Furthermore, there was a close correlation between the expression of isoform VEGF165 and that of its receptors KDR and neuropilin-1. Morphometric analysis demonstrated that the vascular density is significantly higher in the RA synovial tissues with expression of VEGF165, KDR, and neuropilin-1 than in those without their expression (p<0.01). In situ hybridization and immunohistochemical studies indicated that the cells expressing VEGF are macrophage-like synovial lining cells and spindle-shaped cells in the sublining cell layer. These results suggest that the selective up-regulation of the isoform VEGF165 and its signalling via KDR and neuropilin-1 play an important role in the synovial angiogenesis which occurs in RA. Copyright (C) 2000 John Wiley and Sons, Ltd.

AB - Angiogenesis is an indispensable process in the chronic proliferative synovitis and pannus formation of rheumatoid arthritis (RA). Tiffs study examined the expression of vascular endothelial growth factor (VEGF) isoforms and VEGF receptors, Flt-l, KDR and neuropiiin-1, in RA and osteoarthritis (OA) synovia, and studied the relationship between their expression and the synovial angiogenesis. By RT-PCR analysis, the isoform VEGF121 was constitutively expressed in all the RA (17/17 patients) and OA (8/8 patients) synovia. In contrast, the expression of the isoform VEGF165 was observed in 41% of the RA synovia (7/17 patients), but was undetectable in the OA samples (0/8 patients). The receptor Flt-1 was almost constitutively expressed in RA (15/17 patients) and OA (8/8 patients) synovia, while the expression of KDR was detected in the synovia of six RA patients (6/17 patients; 35%) but none of the OA patients (0/8 patients). The expression of neuropilin-1, an isoform-specific receptor for VEGF165 which enhances the binding of VEGF165 to KDR, was also up-regulated in the same RA synovia that expressed KDR. Furthermore, there was a close correlation between the expression of isoform VEGF165 and that of its receptors KDR and neuropilin-1. Morphometric analysis demonstrated that the vascular density is significantly higher in the RA synovial tissues with expression of VEGF165, KDR, and neuropilin-1 than in those without their expression (p<0.01). In situ hybridization and immunohistochemical studies indicated that the cells expressing VEGF are macrophage-like synovial lining cells and spindle-shaped cells in the sublining cell layer. These results suggest that the selective up-regulation of the isoform VEGF165 and its signalling via KDR and neuropilin-1 play an important role in the synovial angiogenesis which occurs in RA. Copyright (C) 2000 John Wiley and Sons, Ltd.

KW - Angiogenesis

KW - Isoform

KW - KDR

KW - Neuropilin-1

KW - Rheumatoid arthritis

KW - VEGF

UR - http://www.scopus.com/inward/record.url?scp=0033841718&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033841718&partnerID=8YFLogxK

M3 - Article

C2 - 10918218

AN - SCOPUS:0033841718

VL - 191

SP - 426

EP - 433

JO - Journal of Pathology

JF - Journal of Pathology

SN - 0022-3417

IS - 4

ER -