Open Access

Neat1 regulates oxidized low-density lipoprotein-induced inflammation and lipid uptake in macrophages via paraspeckle formation

  • Authors:
    • Ning Huang‑Fu
    • Jing‑Song Cheng
    • Yong Wang
    • Zhen‑Wei Li
    • Sheng‑Huang Wang
  • View Affiliations

  • Published online on: December 7, 2017     https://doi.org/10.3892/mmr.2017.8211
  • Pages:3092-3098
  • Copyright: © Huang‑Fu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Oxidized low-density lipoprotein (oxLDL) indu­ces macrophage inflammation and lipid uptake, and serves important roles in the development of atherosclerosis. The long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (neat1) has two isoforms; the longer isoform, neat1_2, mediates the formation of subnuclear structures called paraspeckles. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), western blotting and RNA protein immunoprecipitation (RIP), revealed that oxLDL induced paraspeckle formation in the THP‑1 cell line. Additionally, the nuclear factor‑κB and p38 pathways were observed to be involved in neat1 transcription. To investigate the role of paraspeckles in oxLDL‑induced macrophage inflammation and lipid uptake, macrophages were transfected with small interfering RNAs against NEAT1, NEAT1_2, non‑POU domain-containing octamer-binding (NONO) and splicing factor proline and glutamine rich prior to oxLDL incubation. In addition, inflammation‑associated pathways and scavenger receptors were analyzed by performing western blotting and RT‑qPCR. p65 phosphorylation and cluster of differentiation 36 (CD36) were demonstrated to serve roles in paraspeckle‑mediated inflammation and lipid uptake, respectively. To determine the underlying mechanism, RIP was preformed, which revealed that NONO binds CD36 mRNA to decrease its expression. In conclusion, oxLDL induced neat1_2‑mediated paraspeckle formation. Paraspeckles participate in oxLDL‑induced macrophage inflammation and lipid uptake by regulating p65 phosphorylation and CD36 mRNA.

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February 2018
Volume 17 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

2016 Impact Factor: 1.692
Ranked #19/128 Medicine Research and Experimental
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APA
Huang‑Fu, N., Cheng, J., Wang, Y., Li, Z., & Wang, S. (2018). Neat1 regulates oxidized low-density lipoprotein-induced inflammation and lipid uptake in macrophages via paraspeckle formation. Molecular Medicine Reports, 17, 3092-3098. https://doi.org/10.3892/mmr.2017.8211
MLA
Huang‑Fu, N., Cheng, J., Wang, Y., Li, Z., Wang, S."Neat1 regulates oxidized low-density lipoprotein-induced inflammation and lipid uptake in macrophages via paraspeckle formation". Molecular Medicine Reports 17.2 (2018): 3092-3098.
Chicago
Huang‑Fu, N., Cheng, J., Wang, Y., Li, Z., Wang, S."Neat1 regulates oxidized low-density lipoprotein-induced inflammation and lipid uptake in macrophages via paraspeckle formation". Molecular Medicine Reports 17, no. 2 (2018): 3092-3098. https://doi.org/10.3892/mmr.2017.8211