CLC number:
On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 2023-11-15
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Citations: Bibtex RefMan EndNote GB/T7714
Fang LIU, Shirui CHEN, Xinyue MING, Huijuan LI, Zhaoming ZENG, Yuncheng LV. Sortilin-induced lipid accumulation and atherogenesis are suppressed by HNF1b SUMOylation promoted by flavone of Polygonatum odoratum[J]. Journal of Zhejiang University Science B, 2023, 24(11): 998-1013.
@article{title="Sortilin-induced lipid accumulation and atherogenesis are suppressed by HNF1b SUMOylation promoted by flavone of Polygonatum odoratum",
author="Fang LIU, Shirui CHEN, Xinyue MING, Huijuan LI, Zhaoming ZENG, Yuncheng LV",
journal="Journal of Zhejiang University Science B",
volume="24",
number="11",
pages="998-1013",
year="2023",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2200682"
}
%0 Journal Article
%T Sortilin-induced lipid accumulation and atherogenesis are suppressed by HNF1b SUMOylation promoted by flavone of Polygonatum odoratum
%A Fang LIU
%A Shirui CHEN
%A Xinyue MING
%A Huijuan LI
%A Zhaoming ZENG
%A Yuncheng LV
%J Journal of Zhejiang University SCIENCE B
%V 24
%N 11
%P 998-1013
%@ 1673-1581
%D 2023
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200682
TY - JOUR
T1 - Sortilin-induced lipid accumulation and atherogenesis are suppressed by HNF1b SUMOylation promoted by flavone of Polygonatum odoratum
A1 - Fang LIU
A1 - Shirui CHEN
A1 - Xinyue MING
A1 - Huijuan LI
A1 - Zhaoming ZENG
A1 - Yuncheng LV
J0 - Journal of Zhejiang University Science B
VL - 24
IS - 11
SP - 998
EP - 1013
%@ 1673-1581
Y1 - 2023
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2200682
Abstract: This study aims to investigate the impact of hepatocyte nuclear factor 1β; (HNF1b) on macrophage sortilin-mediated lipid metabolism and aortic atherosclerosis and explore the role of the flavone of Polygonatum odoratum (PAOA-flavone)-promoted small ubiquitin-related modifier (SUMO) modification in the atheroprotective efficacy of HNF1b. HNF1b was predicted to be a transcriptional regulator of sortilin expression via bioinformatics, dual-luciferase reporter gene assay, and chromatin immunoprecipitation. HNF1b overexpression decreased sortilin expression and cellular lipid contents in THP-1 macrophages, leading to a depression in atherosclerotic plaque formation in low-density lipoprotein (LDL) receptor-deficient (LDLR-/-) mice. Multiple SUMO1-modified sites were identified on the HNF1b protein and co-immunoprecipitation confirmed its SUMO1 modification. The SUMOylation of HNF1b protein enhanced the HNF1b-inhibited effect on sortilin expression and reduced lipid contents in macrophages. PAOA-flavone treatment promoted SUMO-activating enzyme subunit 1 (SAE1) expression and SAE1-catalyzed SUMOylation of the HNF1b protein, which prevented sortilin-mediated lipid accumulation in macrophages and the formation of atherosclerotic plaques in apolipoprotein E-deficient (ApoE-/-) mice. Interference with SAE1 abrogated the improvement in lipid metabolism in macrophage cells and atheroprotective efficacy in vivo upon PAOA-flavone administration. In summary, HNF1b transcriptionally suppressed sortilin expression and macrophage lipid accumulation to inhibit aortic lipid deposition and the development of atherosclerosis. This anti-atherosclerotic effect was enhanced by PAOA-flavone-facilitated, SAE1-catalyzed SUMOylation of the HNF1b protein.
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