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Series GSE185754 Query DataSets for GSE185754
Status Public on Oct 15, 2021
Title Cardiomyocyte TLR4 regulates autophagy through TRAF6-mediated TFEB ubiquitination in sepsis-associated cardiac dysfunction
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Sepsis-associated cardiac dysfunction (SACD) is the predominant cause of death in sepsis patients with undefined mechanism of inflammation-autophagy interaction to date. Herein, time-course analysis of cardiac autophagy was conducted in a mouse model of SCAD. An in vitro model established by Lipopolysaccharide-induced macrophage conditioned media stimulation on cardiomyocytes was further investigated for molecular insights. We show cardiomyocyte Toll-like receptor 4 (cTLR4) serves as a central receptor mediating the crosstalk between cardiomyocyte and macrophage, and activation of cTLR4 intensifies the impairment of autophagic flux in cardiomyocytes. Mechanistically, the activation of cTLR4 inactivates TFEB, which largely depends on the E3 ligase activity of TRAF6. Moreover, computational simulation combined with experimental validation revealed the unique local electrostatic interactions between TRAF6 and TFEB. Collectively, our results highlight a previously undescribed role of cTLR4-TRAF6-TFEB signaling in modulating cardiac injury and identify the TRAF6-binding motif in TFEB as an attractive target for SACD therapy.
 
Overall design Cardiac mRNA profiles of saline-injected control mice and LPS-stressed 24 h mice
 
Contributor(s) Wang X, Gao S, Wang Y, Wang W
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Oct 12, 2021
Last update date Oct 15, 2021
Contact name Xiaoping Wang
E-mail(s) XiaopingWang726@outlook.com
Phone +8617702206558
Organization name Beijing University of Chinese Medicine
Street address No. 11, North 3rd Ring East Road, Chaoyang District, Beijing
City Beijing
State/province Beijing
ZIP/Postal code 100029
Country China
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (10)
GSM5623241 heart, saline-injected control mice_1
GSM5623242 heart, saline-injected control mice_2
GSM5623243 heart, saline-injected control mice_3
Relations
BioProject PRJNA770670
SRA SRP341052

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
GSE185754_LPS_24hvsSaline_Reactome_enrich.txt.gz 211.8 Kb (ftp)(http) TXT
GSE185754_Raw_gene_counts_matrix.txt.gz 3.5 Mb (ftp)(http) TXT
GSE185754_Union_for_PCA.txt.gz 354.3 Kb (ftp)(http) TXT
GSE185754_Union_for_tlr4_pathway_cluster.txt.gz 2.6 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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