Knockdown of lncRNA NORAD inhibits the proliferation, inflammation and fibrosis of human mesangial cells under high‑glucose conditions by regulating the miR‑485/NRF1 axis

  • Authors:
    • Linna Wang
    • Xiaoying Yuan
    • Lifeng Lian
    • Huali Guo
    • Hongxia Zhang
    • Minghui Zhang
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  • Published online on: June 14, 2021     https://doi.org/10.3892/etm.2021.10306
  • Article Number: 874
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Abstract

Long non‑coding RNAs (lncRNAs) serve major roles in diabetic nephropathy (DN). The present study investigated the regulatory mechanism of lncRNA non‑coding RNA activated by DNA damage (NORAD) on DN in vitro. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to detect the expression of lncRNA NORAD, microRNA‑485 (miR‑485) and nuclear respiratory factor 1 (NRF1) in the tissues of patients with DN and high‑glucose (HG)‑induced human mesangial cells (HMCs). The viability of HMCs was determined using an MTT assay. The levels of inflammatory [tumour necrosis factor (TNF)‑α, interleukin (IL)‑1β and IL‑6] and fibrotic [type IV collagen (Col. IV), fibronectin (FN) and plasminogen activator inhibitor 1 (PAI‑1)] factors in HMCs were measured by ELISA. The interactions between miR‑485 and NORAD/NRF1 were predicted using StarBase and miRDB softwares and confirmed by a dual‑luciferase reporter assay. Western blot analysis was utilized to measure NRF1 protein levels. lncRNA NORAD was highly expressed in tissues and HG‑induced HMCs. NORAD knockdown suppressed cell viability in HG‑induced HMCs. The levels of the inflammatory and fibrotic factors in HG‑induced HMCs were inhibited by NORAD knockdown. miR‑485 was the direct target of NORAD. NORAD reversed the inhibitory effects of miR‑485 on HG‑induced HMCs. Furthermore, NRF1 was the target gene of miR‑485. Downregulation of miR‑485 and upregulation of NRF1 reversed the inhibitory effects of NORAD knockdown on HG‑induced HMCs. NORAD knockdown inhibited HG‑induced HMC proliferation, inflammation and fibrosis by regulating miR‑485/NRF1, providing a possible therapeutic strategy for DN.
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August-2021
Volume 22 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Wang L, Yuan X, Lian L, Guo H, Zhang H and Zhang M: Knockdown of lncRNA NORAD inhibits the proliferation, inflammation and fibrosis of human mesangial cells under high‑glucose conditions by regulating the miR‑485/NRF1 axis. Exp Ther Med 22: 874, 2021
APA
Wang, L., Yuan, X., Lian, L., Guo, H., Zhang, H., & Zhang, M. (2021). Knockdown of lncRNA NORAD inhibits the proliferation, inflammation and fibrosis of human mesangial cells under high‑glucose conditions by regulating the miR‑485/NRF1 axis. Experimental and Therapeutic Medicine, 22, 874. https://doi.org/10.3892/etm.2021.10306
MLA
Wang, L., Yuan, X., Lian, L., Guo, H., Zhang, H., Zhang, M."Knockdown of lncRNA NORAD inhibits the proliferation, inflammation and fibrosis of human mesangial cells under high‑glucose conditions by regulating the miR‑485/NRF1 axis". Experimental and Therapeutic Medicine 22.2 (2021): 874.
Chicago
Wang, L., Yuan, X., Lian, L., Guo, H., Zhang, H., Zhang, M."Knockdown of lncRNA NORAD inhibits the proliferation, inflammation and fibrosis of human mesangial cells under high‑glucose conditions by regulating the miR‑485/NRF1 axis". Experimental and Therapeutic Medicine 22, no. 2 (2021): 874. https://doi.org/10.3892/etm.2021.10306