Effect of ApoA4 on SERPINA3 mediated by nuclear receptors NR4A1 and NR1D1 in hepatocytes

ApoA4 exerts anti-inflammatory effects, but the mechanism remains unclear. SERPINA3 is a member of the serine proteinase inhibitor gene family, and has been shown to be involved in anti-inflammation and associated with a number of human diseases. In this study, we revealed that ApoA4 stimulates the...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2017-05, Vol.487 (2), p.327-332
Main Authors: Zhang, Yupeng, He, Jing, Zhao, Jing, Xu, Min, Lou, Danwen, Tso, Patrick, Li, Zongfang, Li, Xiaoming
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Animals
ApoA4
Apolipoproteins A - pharmacology
DISEASES
GENES
Hepatocytes - drug effects
Hepatocytes - metabolism
Inflammation
Liver - drug effects
Liver - metabolism
LIVER CELLS
Male
Metabolic Clearance Rate
Mice
Mice, Inbred C57BL
NR1D1
NR4A1
Nuclear Receptor Subfamily 1, Group D, Member 1 - metabolism
Nuclear Receptor Subfamily 4, Group A, Member 1 - metabolism
Organ Specificity - physiology
RECEPTORS
SERINE PROTEINASES
SERPINA3
Serpins - metabolism
TIME DEPENDENCE
Tissue Distribution
VISIBLE RADIATION
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Summary:ApoA4 exerts anti-inflammatory effects, but the mechanism remains unclear. SERPINA3 is a member of the serine proteinase inhibitor gene family, and has been shown to be involved in anti-inflammation and associated with a number of human diseases. In this study, we revealed that ApoA4 stimulates the gene expression of SERPINA3 in mouse hepatocytes both in vivo and in vitro, in a dose- and time-dependent manner. The transcriptional response of SERPINA3 to ApoA4 is regulated through the binding of ApoA4 with nuclear receptors NR4A1 and NR1D1 on the SERPINA3 promoter, which was verified with ChIP, Luciferase activity assay and RNA interference-mediated NR4A1 or NR1D1 gene knockdown. These data suggests that ApoA4 transcriptionally induced SERPINA3 expression via NR1D1 and NR4A1. Our findings may throw light on the function of ApoA4 in inflammatory responses and acute-phase reactions, as well as the development of SERPINA3 relative diseases. •ApoA4 stimulates the expression of SERPINA3 in hepatocytes.•The mechanism works through ApoA4 on the transcription of SERPINA3 via NR4A1 and NR1D1.•ApoA4 may act as an anti-inflammatory response in SERPINA3 relative diseases.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2017.04.058