Date: Monday, November 9, 2015
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
The semaphorin family is a large group of proteins initially described as axon guidance molecules that play crucial roles in the development of the nervous system. However, semaphorins also play a role in other processes such as the regulation of immunity, angiogenesis, apoptosis and cell migration and invasion. Moreover, semaphorins have been related with the pathogenesis of diseases like multiple sclerosis, myocarditis, atherosclerosis and cancer. Importantly, class 3 semaphorins Sema3B and Sema3F have been defined as important tumor suppressors. However, the potential role of class 3 semaphorins in rheumatoid arthritis (RA) remains unknown.
The aim of this study is analyze the role of class 3 semaphorins in the pathology of RA.
Methods: mRNA expression of class 3 semaphorins in the synovial tissue of early, DMARD-naive arthritis patients was analyzed by low-density (q)uantitative PCR array. RA FLS were stimulated for 4h with IL-1β (1 ng/ml), TNF (10 ng/ml) or LPS (1 μg/ml). RNA was isolated, transcribed to mRNA and expression of class 3 semaphorins was analyzed by qPCR. FLS were stimulated with Sema3A, Sema3B or Sema3F (100 ng/ml) in the presence or absence of PDGF (10 ng/ml) and cell migration and invasion were determined using wound closure motility and transwell invasion assays, respectively.
Results: mRNA expression of class 3 semaphorins in the synovial tissue of early arthritis patients negatively and significantly correlated with the mRNA expression of inflammatory mediators and the disease activity parameters of these patients. Moreover, Sema3B, Sema3C, Sema3F and Sema3G mRNA expression was significantly lower in early arthritis patients who developed persistent diseases compared with patients with self-limiting disease after two year follow-up. Also, Sema3F and Sema3B expression was significantly lower in the patients that after 2 years of follow-up progressed to RA compared to those who remained as undifferentiated arthritis patients. FLS expression of Sema3A was significantly induced after IL-1, TNF or LPS stimulation, while the expression of Sema3B and Sema3F was down-regulated. Finally, functional assays showed that Sema3A significantly induced the migration and invasion of FLS. In contrast, Sema3B and Sema3F reduced spontaneous FLS migration and PDGF-induced cell invasion.
Conclusion: these data show that class 3 semaphorins are differently expressed in the synovium of early patients depending of the severity and the progression of the disease and that Sema3A, Sema3B and Sema3F play an important role in the invasiveness ability of RA FLS. Together, class 3 semaphorins and their receptors could be useful biomarkers and promising therapeutic targets for the treatment of RA.
To cite this abstract in AMA style:Garcia Perez S, Malvar Fernandez B, Newsom SP, Tang MW, Radstake TRDJ, Baeten D, Tak PP, Reedquist KA. Class 3 Semaphorins Modulate the Invasive Capacity of Rheumatoid Arthritis Fibroblast-like Synoviocytes [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/class-3-semaphorins-modulate-the-invasive-capacity-of-rheumatoid-arthritis-fibroblast-like-synoviocytes/. Accessed October 28, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/class-3-semaphorins-modulate-the-invasive-capacity-of-rheumatoid-arthritis-fibroblast-like-synoviocytes/