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LncRNA NEAT1 accelerates renal mesangial cell injury via modulating the miR-146b/TRAF6/NF-κB axis in lupus nephritis

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Abstract

Although growing advances have been made in the regulation of lupus nephritis recently, lupus nephritis is still one of the major causes of death in SLE patients and the pathogenesis remains largely unknown. Therefore, exploring the pathological mechanisms is urgently needed for designing and developing novel therapeutic strategies for lupus nephritis. Human renal mesangial cells (HRMCs) were transfected with sh-NEAT1, miR-146b mimic, pcDNA-NEAT1, miR-146b inhibitor, or sh-TRAF6 to modify their expression. Lipopolysaccharide (LPS) was used to induce inflammatory injury. Cell viability was examined with CCK8. Apoptosis was determined by flow cytometry and Hoechst staining. qRT-PCR and western blot were used to analyze gene expression. The secretion of inflammatory cytokines was examined with ELISA. The bindings of NEAT1 with miR-146b and miR-146b with TRAF6 were tested by dual-luciferase reporter assay. NEAT1 was upregulated in LPS-treated HRMCs. Both the knockdown of NEAT1 and TRAF6 suppressed the LPS-induced inflammatory injury in HRMCs. NEAT1 directly targeted miR-146b to control miR-146b-mediated regulation of TRAF6 expression in HRMCs. NEAT1 promoted the expression of TRAF6 via targeting miR-146b to accelerate the LPS-mediated renal mesangial cell injury in HRMCs. Moreover, TRAF6 activated the NF-κB signaling in HRMCs. NEAT1 accelerated renal mesangial cell injury via directly targeting miR-146b, promoting the expression of TRAF6, and activating the NF-κB signaling in lupus nephritis. Our investigation elucidated novel pathological mechanisms and provided potential therapeutic targets for lupus nephritis.

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Funding

This work was supported by a grant from Natural Science Foundation of Hunan Province (2018JJ6017), Hunan Provincial Health Planning Commission Research Project (B20180563).

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Authors and Affiliations

  1. Department of Rheumatology and Immunology, Hunan Provincial People’s Hospital (The First-Affiliated Hospital of Hunan Normal University), No.89, Guhan Road, Furong District, Changsha, 410016, Hunan Province, People’s Republic of China

    Li-Hua Zhang, Bin Xiao, Miao Zhong, Qiao Li, Jian-Ying Chen, Jie-Rou Huang & Hui Rao

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  1. Li-Hua Zhang
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  2. Bin Xiao
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  3. Miao Zhong
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  4. Qiao Li
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  7. Hui Rao
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Correspondence to Hui Rao.

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Written informed permission was obtained from the patients and healthy donors. This study was approved by the Ethics Committee of Hunan Provincial People’s Hospital/The First Affiliated Hospital of Hunan Normal University.

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Zhang, LH., Xiao, B., Zhong, M. et al. LncRNA NEAT1 accelerates renal mesangial cell injury via modulating the miR-146b/TRAF6/NF-κB axis in lupus nephritis. Cell Tissue Res 382, 627–638 (2020). https://doi.org/10.1007/s00441-020-03248-z

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