Date: Monday, November 6, 2017
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Long noncoding RNAs (lncRNAs) have recently been identified to be tightly linked to diverse human diseases. Systemic lupus erythematosus (SLE) is a common autoimmune disease. Renal involvement is the most frequent and serious complication. Type I interferon (I IFN) and a group of inflammatory cytokines induced by type I IFN in human renal mesangial cells(HRMCs) play a vital role in lupus nephritis(LN). In this study we screened and investigated the contribution of the lncRNA RP11-2B6.2 to the pathogenesis of LN involved in the abnormal activation of type I IFN pathway.
The high throughput RNA-seq data from kidney biopsies of LN patients and controls was applied to screen for candidate lncRNA and confirm its relationship with clinical data. Rapid amplification of cDNA ends (RACE) was adopted to identify the full length and exact sequences of lncRNA. In situ hybridization was adopted to identify the lncRNA location of cell nucleus and cytoplasm. Quantitative real-time polymerase chain reaction(RT-qPCR) and western blotting was used to detect the RNA and protein expression of lncRNA and individual genes relevant to type I IFN pathway respectively. Dual-luciferace reporter assay was used to detect the promoter transcriptional activity of genes.
The expression of lncRNA RP11-2B6.2 was significantly increased in the kidney tissues from LN patients compared with those from healthy controls, and positively correlated with the degree of disease activity and renal injury. Additionally, the expression of LncRNA RP11-2B6.2 can be stimulated by type I IFN. Silencing RP11-2B6.2 significantly reduced the expression of a group of interferon-stimulating genes(ISGs) including IFIT1, OAS1, etc., Furthermore, lncRNA RP11-2B6.2 affected the expression of IFN alpha and beta receptor subunit 1 (IFNAR1) and its promoter transcriptional activity, phosphorylation of Jak1 and Stat1, and the luciferase activity induced by interferon stimulated response element(ISRE).
Long noncoding RNA RP11-2B6.2 is a positive regulator of the type I IFN signaling pathway in LN. LncRNA RP11-2B6.2 may contribute to the pathogenesis of LN and provide a potentially therapeutic target.
To cite this abstract in AMA style:Tang Y, Liao Z, Xue Z, Wu L, Shen N. Identification of Long Noncoding RNA RP11-2B6.2 As a Positive Regulator through Type I Interferon Pathway in Lupus Nephritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/identification-of-long-noncoding-rna-rp11-2b6-2-as-a-positive-regulator-through-type-i-interferon-pathway-in-lupus-nephritis/. Accessed August 11, 2020.
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