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Series GSE172283 Query DataSets for GSE172283
Status Public on Apr 19, 2021
Title Loss of Down syndrome critical region-1 leads to cholesterol metabolic dysfunction that exaggerates hypercholesterolemia in ApoE-null background
Organism Mus musculus
Experiment type Expression profiling by array
Summary Down syndrome critical region (DSCR)-1functions as a feedback modulator for calcineurin- nuclear factor for activated T cell(NFAT) signals, which are crucial for cell proliferation and inflammation. Stable expression of DSCR-1 inhibits pathological angiogenesis and septic inflammation. DSCR-1 also plays a critical role in vascular wall remodeling associated with aneurysm development that occurs primarily in smooth muscle cells. Besides, Dscr-1 deficiency promotes the M1-to M2-like phenotypic switch in macrophages, which correlates to the reduction of denatured cholesterol uptakes. However, the distinct roles of DSCR-1 in cholesterol and lipid metabolism are not well understood. Here, we show that loss of apolipoprotein (Apo) E in mice with chronic hypercholesterolemia induced Dscr-1expression in the liver and aortic atheroma. InDscr-1-null mice fed a high-fat diet, oxidative- and endoplasmic reticulum (ER)-stress was induced and sterol regulatory element-binding protein (SREBP) 2production in hepatocytes was stimulated. This exaggerated ApoE-/--mediated nonalcoholic fatty liver disease (NAFLD) and subsequent hypercholesterolemia. Genome wide screening revealed that loss of both ApoE and Dscr-1 resulted in the induction of immune- and leukocyte activation-related genes in the liver compared to ApoE deficiency alone. However, expression of inflammation-activated markers and levels of monocyte adhesion were suspended upon induction of the Dscr-1 null background in the aortic endothelium. Collectively, our study shows that the combined loss of Dscr-1 and ApoE causes metabolic dysfunction in the liver but reduces atherosclerotic plaques, thereby leading to a dramatic increase in serum cholesterol and the formation of sporadic vasculopathy.
 
Overall design We analyzed genome wide gene expression of liver among wild type, Dscr-1 knockout, ApoE knockout and Dscr-1; ApoE double-knockout mice with two independent experiments. Sample number was 8 samples. In these experiments, wild type was used as control. Moreover, we analyzed endothelial cells derived from aorta of Dscr-1 knockout mice or Dscr-1; ApoE double -knockout mice with two independent experiments. Sample number was four. In thees experiments, Dscr-1 was used as control.
 
Contributor(s) Muramatsu M, Osawa T, Miyamura Y, Nakagawa S, Tanaka T, Kodama T, Aburatani H, Sakai J, Ryeom S, Minami T
Citation(s) 33895138
Submission date Apr 18, 2021
Last update date Jul 20, 2021
Contact name Takashi Minami
E-mail(s) t-minami@kumamoto-u.ac.jp
Organization name Kumamoto University
Street address 2-2-1, Honjo
City Kumamoto
ZIP/Postal code 860-0811
Country Japan
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (12)
GSM5251822 Liver_WT_rep1
GSM5251823 Liver_WT_rep2
GSM5251824 Liver_Dscr-1-KO_rep1
Relations
BioProject PRJNA722746

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE172283_RAW.tar 59.2 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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