التفاصيل البيبلوغرافية
| العنوان: |
Targeting non-canonical nuclear factor-κB signalling attenuates neovascularization in a novel 3D model of rheumatoid arthritis synovial angiogenesis. |
| المؤلفون: |
Maracle, Chrissta X., Kucharzewska, Paulina, Helder, Boy, van der Horst, Corine, de Sampaio, Pedro Correa, Ae-Ri Noort, van Zoest, Katinka, Griffioen, Arjan W., Olsson, Henric, Tas, Sander W. |
| المصدر: |
Rheumatology; Feb2017, Vol. 56 Issue 2, p294-302, 9p, 4 Graphs |
| مصطلحات موضوعية: |
CELLULAR signal transduction, ENZYME-linked immunosorbent assay, GROWTH factors, MICROSCOPY, NEOVASCULARIZATION, PROTEIN kinases, RESEARCH funding, RHEUMATOID arthritis, RNA, SYNOVIAL fluid, T-test (Statistics), THREE-dimensional imaging, DISEASE progression, DESCRIPTIVE statistics, IN vitro studies |
| مستخلص: |
Objective. Angiogenesis is crucial in RA disease progression. Lymphotoxin β receptor (LTβR)-induced activation of the non-canonical nuclear factor-κB (NF-κB) pathway via NF-κB-inducing kinase (NIK) has been implicated in this process. Consequently, inhibition of this pathway may hold therapeutic potential in RA. We describe a novel three-dimensional (3D) model of synovial angiogenesis incorporating endothelial cells (ECs), RA fibroblast-like synoviocytes (RAFLSs) and RA synovial fluid (RASF) to further investigate the contributions of NF-κB in this process. Methods. Spheroids consisting of RAFLSs and ECs were stimulated with RASF, the LTβR ligands LTβ and LIGHT, or growth factor bFGF and VEGF, followed by quantification of EC sprouting using confocal microscopy and digital image analysis. Next, the effects of anginex, NIK-targeting siRNA (siNIK), LTβR-lg fusion protein (baminercept) and a novel pharmacological NIK inhibitor were investigated. Results. RASF significantly promoted sprout formation, which was blocked by the established angiogenesis inhibitor anginex (P < 0.05). LTβ and LIGHT induced significant sprouting (P < 0.05), as did bFGF/VEGF (P < 0.01). siNIK pre-treatment of ECs led to reductions in LTβR-induced vessel formation (P < 0.05). LTβR-lg not only blocked LTβ- or LIGHT-induced sprouting, but also RASF-induced sprouting (P < 0.05). The NIK inhibitor blocked angiogenesis induced by LTβ, LIGHT, growth factors (P < 0.05) and RASF (P < 0.01). Conclusion. We present a novel 3D model of synovial angiogenesis incorporating RAFLSs, ECs and RASF that mimics the in vivo situation. Using this system, we demonstrate that non-canonical NF-κB signalling promotes neovascularization and show that this model is useful for dissecting relative contributions of signalling pathways in specific cell types to angiogenic responses and for testing pharmacological inhibitors of angiogenesis. [ABSTRACT FROM AUTHOR] |
|
Copyright of Rheumatology is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder