Background: Ankylosing spondylitis (AS; OMIM:106300) is a common complex inflammatory disease; in a previous study, we introduced a novel mutation in the gene (OMIM: 600514) which was associated with AS. This study is designed to investigate the potential effect of S2486G mutation on reelin secretion; additionally, we objected to evaluate the phospholipase A2 () gene (OMIM: 601690) expression and platelet-activating factor-acetylhydrolase (PAF-AH) concentration as the downstream gene and the encoded protein.
Methods: The impact of the S2486G on reelin protein secretion was investigated in CHO-K1 and HEK-293T cells by constructing wild-type and mutant plasmids. Besides, the possible effect of the mutation on expression and concentration of and PAF-AH in THP1 cells was assessed by quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The study was performed at Tarbiat Modares University, Tehran, Iran, from 2016 to 2018.
Results: Our results showed that S2486G not only causes a significant reduction in reelin secretion in both HEK-293T and CHO-K1 cells, but also it leads to a significant reduction in gene expression ( value < 0.001) and protein level of PAF-AH in THP-1 cells ( value < 0.003).
Conclusion: The S2486G mutation in can alter inflammatory and, to some extent, osteogenesis pathways mediated by reduced secretion of reelin and also reduced expression of the gene.
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http://dx.doi.org/10.34172/aim.2020.87 | DOI Listing |
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