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 language | English |
|---|---|
| Pages (from-to) | 426-433 |
| Number of pages | 8 |
| Journal | Journal of Pathology |
| Volume | 191 |
| Issue number | 4 |
| Publication status | Published - 2000 |
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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 journal › Article
}
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 -