Piceatannol inhibits pyroptosis and suppresses oxLDL-induced lipid storage in macrophages by regulating miR-200a/Nrf2/GSDMD axis.
Animals
Atherosclerosis
/ drug therapy
Caspase 1
/ metabolism
Drug Evaluation, Preclinical
Gene Knockdown Techniques
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
Lipoproteins, LDL
/ metabolism
Mice
MicroRNAs
/ agonists
NF-E2-Related Factor 2
/ genetics
Phosphate-Binding Proteins
/ genetics
Pyroptosis
/ drug effects
RAW 264.7 Cells
RNA, Small Interfering
/ metabolism
Signal Transduction
/ drug effects
Stilbenes
/ pharmacology
GSDMD
atherosclerosis
miR-200a
nrf2
piceatannol
pyroptosis
Journal
Bioscience reports
ISSN: 1573-4935
Titre abrégé: Biosci Rep
Pays: England
ID NLM: 8102797
Informations de publication
Date de publication:
30 09 2020
30 09 2020
Historique:
received:
25
04
2020
revised:
01
09
2020
accepted:
03
09
2020
pubmed:
5
9
2020
medline:
30
3
2021
entrez:
5
9
2020
Statut:
ppublish
Résumé
As a major bioactive compound from grapes, piceatannol (PIC) has been reported to exert anti-atherosclerotic activity in various studies. Nevertheless, the mechanism underlying the effect of piceatannol against atherosclerosis (AS) is elusive. Our study identified miR-200a/Nrf2/GSDMD signaling pathway as critical mediators in the effect of piceatannol on macrophages. In the present study, we confirmed that treatment of piceatannol repressed the oxLDL-induced lipid storage in macrophages. Compared with control group, piceatannol inhibited TG storage and the activity of caspase1. It is noting that in response to oxLDL challenge, piceatannol abated the pyroptosis in RAW264.7 cells, with a decreased expression of caspase1, gasdermin D (GSDMD), IL-18, IL-1β and NLRP3. Moreover, we investigated the role of microRNA (miR)-200a/Nrf2 signaling pathway in the effect of piceatannol. The results declared that after transfection of si-miR-200a or si-Nrf2 plasmids, the effects of piceatannol on macrophages were converted, including lipid storage and pyroptosis. Importantly, si-miR-200a plasmid reduced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), indicating that miR-200a acted as an enhancer of Nrf2 in macrophages. Collectively, our findings demonstrate that piceatannol exerts anti-atherosclerotic activity on RAW264.7 cells by regulating miR-200a/Nrf2/GSDMD signaling. The present study is the first time to identify miR-200a as a candidate target in AS and declared an association between miR-200a and pyroptosis, which provides a novel therapy for the treatment of AS.
Identifiants
pubmed: 32886103
pii: 226337
doi: 10.1042/BSR20201366
pmc: PMC7494992
pii:
doi:
Substances chimiques
Gsdmd protein, mouse
0
Intracellular Signaling Peptides and Proteins
0
Lipoproteins, LDL
0
MicroRNAs
0
Mirn200 microRNA, mouse
0
NF-E2-Related Factor 2
0
Nfe2l2 protein, mouse
0
Phosphate-Binding Proteins
0
RNA, Small Interfering
0
Stilbenes
0
oxidized low density lipoprotein
0
3,3',4,5'-tetrahydroxystilbene
6KS3LS0D4F
Casp1 protein, mouse
EC 3.4.22.36
Caspase 1
EC 3.4.22.36
Types de publication
Journal Article
Retracted Publication
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : RetractionIn
Informations de copyright
© 2020 The Author(s).
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