Expression of ADAM15 in rheumatoid synovium: up-regulation by vascular endothelial growth factor and possible implications for angiogenesis.

Koichiro Komiya, Hiroyuki Enomoto, Isao Inoki, Satoko Okazaki, Yoshinari Fujita, Eiji Ikeda, Eiko Ohuchi, Hideo Matsumoto, Yoshiaki Toyama, Yasunori Okada

Research output: Contribution to journalArticle

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Abstract

ADAMs (a disintegrin and metalloproteinases) comprise a new gene family of metalloproteinases, and may play roles in cell-cell interaction, cell migration, signal transduction, shedding of membrane-anchored proteins and degradation of extracellular matrix. We screened the mRNA expression of 10 different ADAMs with a putative metalloproteinase motif in synovial tissues from patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Reverse transcription PCR and real-time quantitative PCR analyses indicated that among the ADAMs, ADAM15 mRNA was more frequently expressed in the RA samples and its expression level was significantly 3.8-fold higher in RA than in OA (p < 0.01). In situ hybridization, immunohistochemistry and immunoblotting demonstrated that ADAM15 is expressed in active and precursor forms in the synovial lining cells, endothelial cells of blood vessels and macrophage-like cells in the sublining layer of RA synovium. There was a direct correlation between ADAM15 mRNA expression levels and vascular density in the synovial tissues (r = 0.907, p < 0.001; n = 20). ADAM15 was constitutively expressed in RA synovial fibroblasts and human umbilical vein endothelial cells (HUVECs), and the expression level was increased in HUVECs by treatment with vascular endothelial growth factor (VEGF)165. On the other hand, ADAM15 expression in RA synovial fibroblasts was enhanced with VEGF165 only if vascular endothelial growth factor receptor (VEGFR)-2 expression was induced by treatment with tumor necrosis factor-alpha, and the expression was blocked with SU1498, a specific inhibitor of VEGFR-2. These data demonstrate that ADAM15 is overexpressed in RA synovium and its expression is up-regulated by the action of VEGF165 through VEGFR-2, and suggest the possibility that ADAM15 is involved in angiogenesis in RA synovium.

Original languageEnglish
JournalArthritis research & therapy
Volume7
Issue number6
Publication statusPublished - 2005

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Synovial Membrane
Vascular Endothelial Growth Factor A
Rheumatoid Arthritis
Up-Regulation
Metalloproteases
Disintegrins
Vascular Endothelial Growth Factor Receptor-2
Human Umbilical Vein Endothelial Cells
Osteoarthritis
Messenger RNA
Blood Vessels
Fibroblasts
Immunoblotting
Cell Communication
Proteolysis
Reverse Transcription
Cell Movement
In Situ Hybridization
Extracellular Matrix
Real-Time Polymerase Chain Reaction

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Expression of ADAM15 in rheumatoid synovium : up-regulation by vascular endothelial growth factor and possible implications for angiogenesis. / Komiya, Koichiro; Enomoto, Hiroyuki; Inoki, Isao; Okazaki, Satoko; Fujita, Yoshinari; Ikeda, Eiji; Ohuchi, Eiko; Matsumoto, Hideo; Toyama, Yoshiaki; Okada, Yasunori.

In: Arthritis research & therapy, Vol. 7, No. 6, 2005.

Research output: Contribution to journalArticle

Komiya, K, Enomoto, H, Inoki, I, Okazaki, S, Fujita, Y, Ikeda, E, Ohuchi, E, Matsumoto, H, Toyama, Y & Okada, Y 2005, 'Expression of ADAM15 in rheumatoid synovium: up-regulation by vascular endothelial growth factor and possible implications for angiogenesis.', Arthritis research & therapy, vol. 7, no. 6.
Komiya, Koichiro ; Enomoto, Hiroyuki ; Inoki, Isao ; Okazaki, Satoko ; Fujita, Yoshinari ; Ikeda, Eiji ; Ohuchi, Eiko ; Matsumoto, Hideo ; Toyama, Yoshiaki ; Okada, Yasunori. / Expression of ADAM15 in rheumatoid synovium : up-regulation by vascular endothelial growth factor and possible implications for angiogenesis. In: Arthritis research & therapy. 2005 ; Vol. 7, No. 6.
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AU - Okazaki, Satoko

AU - Fujita, Yoshinari

AU - Ikeda, Eiji

AU - Ohuchi, Eiko

AU - Matsumoto, Hideo

AU - Toyama, Yoshiaki

AU - Okada, Yasunori

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