基因敲除
下调和上调
医学
脂联素
类风湿性关节炎
肿瘤坏死因子α
滑膜
炎症
滑膜关节
关节炎
基因
免疫学
癌症研究
分子生物学
内科学
生物
骨关节炎
胰岛素抵抗
病理
遗传学
胰岛素
替代医学
关节软骨
作者
Sujit Kashyap,Uma Kumar,Anuj Kumar Pandey,Maumita Kanjilal,Patralika Chattopadhyay,Chandrashekhar Yadav,B. K. Thelma
出处
期刊:PubMed
日期:2018-02-22
卷期号:36 (4): 581-588
被引量:1
摘要
ARL15 is a novel susceptibility gene identified in a recent GWAS in a north Indian rheumatoid arthritis (RA) cohort. However, the role of ARL15 or ARF family genes in RA aetiology remains unknown. Therefore, we aimed to i) establish the expression of ARL15 in rheumatoid arthritis synovial fibroblasts (RASF) and ii) its functional characterisation by assessing its effects on major inflammatory cytokines and interacting partners using a knockdown approach.RASF were cultured from synovial tissue obtained from RA patients (n=5) and osteoarthritis (OA) patients (n=3) serving as controls. Expression of ARL15, ARF1 and ARF6 in RASF was checked by semi-quantitative PCR and western blots; and altered expression of ARL15, if any, by induction of RASF with TNF using real-time PCR. The effect of ARL15 on the expression of adiponectin, adiponectin receptor I, IL6 and GAPDH and on cell mobility by invasion and migration assays were assessed by siRNA mediated gene knockdown.Expression of ARL15, ARF1 and ARF6 was confirmed in RASF and OASF samples but ARL15 expression remained unaltered on TNF induction. Notably, ARL15 knockdown resulted in downregulation of IL6 and GAPDH, upregulation of adiponectin and adiponectin receptor I genes; and significant reduction in migration and invasion of RASF. Genemania showed significant interactions of ARL15 with genes responsible for insulin resistance and phospholipase D.This first report on ARL15 expression in RASF and its likely role in inflammation and metabolic syndromes through a TNF independent pathway, encourages hypothesis-free studies to identify additional pathways underlying RA disease biology.
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