Functional Analysis of RELN S2486G Mutation and its Contribution to Pathogenesis of Ankylosing Spondylitis.

Abstract:

BACKGROUND: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. 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 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. 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 PLA2G7 gene expression (P value < 0.001) and protein level of PAF-AH in THP-1 cells (P value < 0.003). CONCLUSION: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.

journal_name

Arch Iran Med

authors

Esmaeilzadeh-Gharehdaghi E,Razmara E,Bitaraf A,Jamshidi A,Mahmoudi M,Garshasbi M

doi

10.34172/aim.2020.87

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

688-696

issue

10

eissn

1029-2977

issn

1735-3947

journal_volume

23

pub_type

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