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A Disintegrin and Metalloprotease 15 is Expressed on Rheumatoid Arthritis Synovial Tissue Endothelial Cells and may Mediate Angiogenesis
A disintegrin and metalloprotease 15 (ADAM15) is involved in several malignancies. In this study, we investigated the role of ADAM15 in rheumatoid arthritis (RA) angiogenesis. Soluble ADAM15 (s-ADAM15) in serum from RA and normal (NL) subjects was measured using ELISA. To determine membrane-anchored...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356746/ https://www.ncbi.nlm.nih.gov/pubmed/30634456 http://dx.doi.org/10.3390/cells8010032 |
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author | Nishimi, Shinichiro Isozaki, Takeo Wakabayashi, Kuninobu Takeuchi, Hiroko Kasama, Tsuyoshi |
author_facet | Nishimi, Shinichiro Isozaki, Takeo Wakabayashi, Kuninobu Takeuchi, Hiroko Kasama, Tsuyoshi |
author_sort | Nishimi, Shinichiro |
collection | PubMed |
description | A disintegrin and metalloprotease 15 (ADAM15) is involved in several malignancies. In this study, we investigated the role of ADAM15 in rheumatoid arthritis (RA) angiogenesis. Soluble ADAM15 (s-ADAM15) in serum from RA and normal (NL) subjects was measured using ELISA. To determine membrane-anchored ADAM15 (ADAM15) expression in RA synovial tissues, immunohistochemistry was performed. To examine the role of ADAM15 in angiogenesis, we performed in vitro Matrigel assays and monocyte adhesion assays using human umbilical vein endothelial cells (HUVECs) transfected with ADAM15 siRNA. Finally, to investigate whether angiogenic mediators were affected by ADAM15, cytokines in ADAM15 siRNA-transfected HUVEC-conditioned medium were measured. ADAM15 was significantly higher in RA serum than in NL serum. ADAM15 was also expressed on RAST endothelial cells. ADAM15 siRNA-treated HUVECs had decreased EC tube formation in response to RA synovial fluids compared with non-treated HUVECs. The adhesion index of ADAM15 siRNA-transfected HUVECs was significantly lower than the adhesion index of control siRNA-transfected HUVECs. ENA-78/CXCL5 and ICAM-1 were decreased in tumor necrosis factor (TNF)-α-stimulated ADAM15 siRNA-transfected HUVEC-conditioned medium compared with TNF-α-stimulated control siRNA-transfected HUVEC-conditioned medium. These data show that ADAM15 plays a role in RA angiogenesis, suggesting that ADAM15 might be a potential target in inflammatory diseases such as RA. |
format | Online Article Text |
id | pubmed-6356746 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63567462019-02-06 A Disintegrin and Metalloprotease 15 is Expressed on Rheumatoid Arthritis Synovial Tissue Endothelial Cells and may Mediate Angiogenesis Nishimi, Shinichiro Isozaki, Takeo Wakabayashi, Kuninobu Takeuchi, Hiroko Kasama, Tsuyoshi Cells Article A disintegrin and metalloprotease 15 (ADAM15) is involved in several malignancies. In this study, we investigated the role of ADAM15 in rheumatoid arthritis (RA) angiogenesis. Soluble ADAM15 (s-ADAM15) in serum from RA and normal (NL) subjects was measured using ELISA. To determine membrane-anchored ADAM15 (ADAM15) expression in RA synovial tissues, immunohistochemistry was performed. To examine the role of ADAM15 in angiogenesis, we performed in vitro Matrigel assays and monocyte adhesion assays using human umbilical vein endothelial cells (HUVECs) transfected with ADAM15 siRNA. Finally, to investigate whether angiogenic mediators were affected by ADAM15, cytokines in ADAM15 siRNA-transfected HUVEC-conditioned medium were measured. ADAM15 was significantly higher in RA serum than in NL serum. ADAM15 was also expressed on RAST endothelial cells. ADAM15 siRNA-treated HUVECs had decreased EC tube formation in response to RA synovial fluids compared with non-treated HUVECs. The adhesion index of ADAM15 siRNA-transfected HUVECs was significantly lower than the adhesion index of control siRNA-transfected HUVECs. ENA-78/CXCL5 and ICAM-1 were decreased in tumor necrosis factor (TNF)-α-stimulated ADAM15 siRNA-transfected HUVEC-conditioned medium compared with TNF-α-stimulated control siRNA-transfected HUVEC-conditioned medium. These data show that ADAM15 plays a role in RA angiogenesis, suggesting that ADAM15 might be a potential target in inflammatory diseases such as RA. MDPI 2019-01-09 /pmc/articles/PMC6356746/ /pubmed/30634456 http://dx.doi.org/10.3390/cells8010032 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nishimi, Shinichiro Isozaki, Takeo Wakabayashi, Kuninobu Takeuchi, Hiroko Kasama, Tsuyoshi A Disintegrin and Metalloprotease 15 is Expressed on Rheumatoid Arthritis Synovial Tissue Endothelial Cells and may Mediate Angiogenesis |
title | A Disintegrin and Metalloprotease 15 is Expressed on Rheumatoid Arthritis Synovial Tissue Endothelial Cells and may Mediate Angiogenesis |
title_full | A Disintegrin and Metalloprotease 15 is Expressed on Rheumatoid Arthritis Synovial Tissue Endothelial Cells and may Mediate Angiogenesis |
title_fullStr | A Disintegrin and Metalloprotease 15 is Expressed on Rheumatoid Arthritis Synovial Tissue Endothelial Cells and may Mediate Angiogenesis |
title_full_unstemmed | A Disintegrin and Metalloprotease 15 is Expressed on Rheumatoid Arthritis Synovial Tissue Endothelial Cells and may Mediate Angiogenesis |
title_short | A Disintegrin and Metalloprotease 15 is Expressed on Rheumatoid Arthritis Synovial Tissue Endothelial Cells and may Mediate Angiogenesis |
title_sort | disintegrin and metalloprotease 15 is expressed on rheumatoid arthritis synovial tissue endothelial cells and may mediate angiogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356746/ https://www.ncbi.nlm.nih.gov/pubmed/30634456 http://dx.doi.org/10.3390/cells8010032 |
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