Abstract
Ankylosing spondylitis (AS; OMIM:106300) is a common complex inflammatory disease; in a previous study, we introduced a novel mutation in the RELN gene (OMIM: 600514) which was associated with AS. This study is designed to investigate the potential effect of RELN S2486G mutation on reelin secretion; additionally, we objected to evaluate the phospholipase A2 (PLA2G7) gene (OMIM: 601690) expression and platelet-activating factor-acetylhydrolase (PAF-AH) concentration as the downstream gene and the encoded protein. 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 PLA2G7 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. 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 PLA2G7 gene expression (P value < 0.001) and protein level of PAF-AH in THP-1 cells (P value < 0.003). The S2486G mutation in RELN can alter inflammatory and, to some extent, osteogenesis pathways mediated by reduced secretion of reelin and also reduced expression of the PLA2G7 gene.
Highlights
Ankylosing spondylitis (AS; OMIM:106300) is a chronic inflammatory disease affecting the skeletal systems, mainly the spine and sacroiliac joints.[1]
We investigated the potential effect of S2486G mutation on reelin secretion; we evaluated its effect on the PLA2G7 gene expression and platelet-activating factor-acetylhydrolase (PAF-AH) concentration by constructing a subregion of Human RELN containing the R5-R6 domains and the C-terminal region (CTR)
We demonstrated that the S2486G mutation leads to a reduction of reelin secretion in CHO-K1 and HEK293T cells, and causes a significant decrease of both the PLA2G7 gene expression and the plateletactivating factor (PAF)-AH protein level in THP-1-monocyte/macrophages cells
Summary
Ankylosing spondylitis (AS; OMIM:106300) is a chronic inflammatory disease affecting the skeletal systems, mainly the spine and sacroiliac joints.[1]. We reported a novel heterozygous mutation in the RELN (OMIM: 600514) gene, c.7456. Ankylosing spondylitis (AS; OMIM:106300) is a common complex inflammatory disease; in a previous study, we introduced a novel mutation in the RELN gene (OMIM: 600514) which was associated with AS. This study is designed to investigate the potential effect of RELN S2486G mutation on reelin secretion; we objected to evaluate the phospholipase A2 (PLA2G7) gene (OMIM: 601690) expression and platelet-activating factor-acetylhydrolase (PAF-AH) concentration as the downstream gene and the encoded protein. Results: Our results showed that S2486G causes a significant reduction in reelin secretion in both HEK-293T and CHO-K1 cells, and it leads to a significant reduction in PLA2G7 gene expression (P value < 0.001) and protein level of PAFAH in THP-1 cells (P value < 0.003).
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