Neat1 regulates oxidized low-density lipoprotein-induced inflammation and lipid uptake in macrophages via paraspeckle formation.
Mol Med Rep
; 17(2): 3092-3098, 2018 Feb.
Article
in En
| MEDLINE
| ID: mdl-29257236
ABSTRACT
Oxidized low-density lipoprotein (oxLDL) indu-ces 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 transcriptionquantitative polymerase chain reaction (RTqPCR), western blotting and RNA protein immunoprecipitation (RIP), revealed that oxLDL induced paraspeckle formation in the THP1 cell line. Additionally, the nuclear factorκB and p38 pathways were observed to be involved in neat1 transcription. To investigate the role of paraspeckles in oxLDLinduced macrophage inflammation and lipid uptake, macrophages were transfected with small interfering RNAs against NEAT1, NEAT1_2, nonPOU domain-containing octamer-binding (NONO) and splicing factor proline and glutamine rich prior to oxLDL incubation. In addition, inflammationassociated pathways and scavenger receptors were analyzed by performing western blotting and RTqPCR. p65 phosphorylation and cluster of differentiation 36 (CD36) were demonstrated to serve roles in paraspecklemediated 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_2mediated paraspeckle formation. Paraspeckles participate in oxLDLinduced macrophage inflammation and lipid uptake by regulating p65 phosphorylation and CD36 mRNA.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Nucleus
/
RNA, Long Noncoding
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Inflammation
/
Lipoproteins, LDL
/
Macrophages
Limits:
Humans
Language:
En
Journal:
Mol Med Rep
Year:
2018
Type:
Article