Long noncoding RNA THRIL promotes foam cell formation and inflammation in macrophages.
Humans
Atherosclerosis
/ metabolism
ATP Binding Cassette Transporter 1
/ metabolism
Cholesterol
/ metabolism
Foam Cells
/ metabolism
Inflammation
/ metabolism
Lipoproteins, LDL
/ metabolism
Macrophages
/ metabolism
RNA, Long Noncoding
/ genetics
Tumor Necrosis Factor-alpha
/ metabolism
Gene Knockdown Techniques
FOXO1
atherosclerosis
cholesterol efflux
inflammation
lipid accumulation
Journal
Cell biology international
ISSN: 1095-8355
Titre abrégé: Cell Biol Int
Pays: England
ID NLM: 9307129
Informations de publication
Date de publication:
Jan 2023
Jan 2023
Historique:
received:
31
07
2022
accepted:
13
09
2022
pubmed:
15
10
2022
medline:
22
12
2022
entrez:
14
10
2022
Statut:
ppublish
Résumé
Tumor necrosis factor-α (TNF-α) and heterogenous nuclear ribonucleoprotein L (hnRNPL)-related immunoregulatory lincRNA (THRIL) is a long noncoding RNA (lncRNA) involved in various inflammatory diseases. However, its role in atherosclerosis is not known. In this study, we aimed to investigate the function of THRIL in mediating macrophage inflammation and foam cell formation. The expression of THRIL was quantified in THP-1 macrophages after treatment with oxidized low-density lipoprotein (oxLDL). The effect of THRIL overexpression and knockdown on oxLDL-induced inflammatory responses and lipid accumulation was determined. THRIL-associated protein partners were identified by RNA pull-down and RNA immunoprecipitation assays. We show that THRIL is upregulated in macrophages after oxLDL treatment. Knockdown of THRIL blocks oxLDL-induced expression of interleukin-1β (IL-1β), IL-6, and TNF-α and lipid accumulation. Conversely, ectopic expression of THRIL enhances inflammatory gene expression and lipid deposition in oxLDL-treated macrophages. Moreover, THRIL depletion increases cholesterol efflux from macrophages and the expression of ATP-binding cassette transporter (ABC) A1 and ABCG1. FOXO1 is identified as a protein partner of THRIL and promotes macrophage inflammation and lipid accumulation. Furthermore, overexpression of FOXO1 restores lipid accumulation and inflammatory cytokine production in THRIL-depleted macrophages. In conclusion, our data suggest a model where THRIL interacts with FOXO1 to promote macrophage inflammation and foam cell formation. THRIL may represent a therapeutic target for atherosclerosis.
Substances chimiques
ATP Binding Cassette Transporter 1
0
Cholesterol
97C5T2UQ7J
Lipoproteins, LDL
0
RNA, Long Noncoding
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
156-166Subventions
Organisme : Basic Research Program of Shanxi Province (Free Exploration) of China
ID : 20210302124416
Organisme : Science and Technology Grant for Selected Returned Chinese Scholars of Shanxi Province of China
ID : 20220043
Informations de copyright
© 2022 International Federation for Cell Biology.
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