The protection of NF‐κB inhibition on kidney injury of systemic lupus erythematosus mice may be correlated with lncRNA TUG1

Abstract

We aimed to know the effect of nuclear factor‐kappa B (NF‐κB) inhibition on the kidney injury of systemic lupus erythematosus (SLE) mice. Pristane‐induced SLE mice were treated with pyrrolidine dithiocarbamate (PDTC, 50 or 100 mg/kg), a NF‐κB inhibitor. Histopathological changes were observed by hematoxylin & eosin, Masson and periodic schiff‐methenamine stainings. Long noncoding RNA Taurine upregulated gene 1 (LncRNA TUG1) was measured by real‐time reverse transcription PCR, NF‐κB p65 expression by western blotting, levels of inflammatory cytokines, antinuclear antibodies (ANA), and antidouble stranded DNA (anti‐dsDNA) by enzyme‐linked immunosorbent assay, and the deposition of IgG and C3 by immunofluorescence. The kidney of SLE mice exhibited interstitial inflammatory cell infiltration, interstitial fibrous proliferation, glomerular mesangial proliferation, and crescent formation, which was mitigated after PDTC administration. The levels of BUN, Cr, ANA, and anti‐dsDNA and the pro‐inflammatory factors in SLE mice were increased with obvious deposition of IgG and C3, but they were also reversed by PDTC. Furthermore, the NF‐κB p65 expression in the nucleus in the SLE mice was decreased with the up‐regulation of TUG1 expression and NF‐κB p65 expression in the cytoplasm after PDTC treatment. Correlation analysis revealed the negative correlation between the TUG1 expression and NF‐κB p65 in the nucleus in the kidney tissues. NF‐κB inhibition with PDTC protected against the kidney injury of pristine‐induced SLE mice possibly via up‐regulating lncRNA TUG1, and further clinical studies are needed to clarify whether NF‐κB inhibition may be a therapeutic modality for the kidney injury of SLE.

Involvement of long noncoding RNAs in the pathogenesis of autoimmune diseases

“…The level of TUG1 is correlated with SLEDAI, ESR, disease duration and 24-h urinary protein [ 111 ]. In a mouse SLE model, TUG1 was observed to be involved in the protective effect of NF-κB inhibition on kidney injury [ 112 ]. Elevated lncRNA RP11-2B6.2 was observed in kidney biopsies from LN patients and positively correlated with disease activity and IFN scores.…”

“… [ 111 ] TUG1 Pyrrolidine dithiocarbamate treated mouse Kidney Upregulated Involved in the protection of NF-kappaB inhibition on kidney injury. [ 112 ] RP11-2B6.2 Human Kidney biopsies from LN patients Up-regulated Regulates IFN-I pathway through epigenetic inhibition of SOCS1. [ 113 ] IMMs lncRNA 7 ​S ​L Human Serum – Autoantibody against lncRNA 7 ​S ​L is related to PM/DM.…”

Exploring the Role of Non-Coding RNAs in the Pathophysiology of Systemic Lupus Erythematosus

“…These results indicate the possibility that linc0949 could serve as a diagnostic marker for SLE that correlates with disease activity [ 24 ]. In an animal model of SLE, the suppression of the NF-κB pathway was shown to exert a protective role against kidney injury [ 25 ]. This effect was suggested to be a result of enhancement of the expression of the lncRNA TUG1 [ 25 ].…”

“…In an animal model of SLE, the suppression of the NF-κB pathway was shown to exert a protective role against kidney injury [ 25 ]. This effect was suggested to be a result of enhancement of the expression of the lncRNA TUG1 [ 25 ]. TUG1 was also found to be downregulated in the PBMCs of SLE patients compared with controls.…”

An integrated analysis of lncRNA and mRNA expression profiles in the kidneys of mice with lupus nephritis

“…Moreover, a number of studies have demonstrated the functional roles of several lncRNAs, including NEAT1, MALAT1, HOXA-AS2, and SLEAR, in SLE according to in vitro loss-of-function and gain-of-function strategies ( Fan et al, 2020 ; Wu et al, 2020 ; Yang et al, 2017 ; Zhang et al, 2016 ). In particular, the lncRNAs THRIL, TUG1 and RP11-2B6.2 were reported to play promotion or inhibition roles in kidney injury in SLE ( Cao et al, 2020 ; Deng et al, 2018 ; Liao et al, 2019 ; Xu, Deng & Zhang, 2018 ). In addition, one study performed RNA-seq to compare the expression levels of lncRNAs in kidney biopsies from patients with LN and patients with kidney tumors ( Liao et al, 2019 ).…”