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Series GSE134950 Query DataSets for GSE134950
Status Public on Aug 29, 2019
Title Mitochondrial damage activates the STING pathway to promote chronic kidney disease
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Fibrosis of the kidney is the final common pathway leading to end stage renal failure. By analyzing kidneys of patients and animal models with fibrosis we observed a significant mitochondrial defect, including the loss of the mitochondrial transcription factor A (TFAM) in kidney tubule cells. Here, we generated mice with tubule-specific deletion of TFAM (Ksp-Cre/Tfam flox/flox). While these mice developed severe mitochondrial loss and energetic deficit (ATP level decline) by 6 weeks of age, kidney fibrosis, immune cell infiltration and progressive azotemia causing death was only observed around 12 weeks of age. Mechanistic studies demonstrated that in the TFAM KO mice aberrant packaging of the mitochondrial DNA (mtDNA) resulted in escape of the mtDNA into the cytosol of the renal cells, activation of the cytosolic cGAS-STING (Stimulator of interferon genes) DNA sensing pathway, and thus cytokine expression and immune cell recruitment. Genetic deletion or pharmacological inhibition of STING ameliorated kidney fibrosis in mouse models of chronic kidney disease, demonstrating that in addition to its essential role in metabolism TFAM sequesters mtDNA to prevent the activation of innate immune pathways and fibrosis.
Overall design RNA-seq of kidneys of 12 weeks old control mice (Tfam flox/flox without Ksp cre) and Kspcre Tfam flox/flox mice
Contributor(s) Ki Wung C, Poonam D, Xin S, Katalin S
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Submission date Jul 26, 2019
Last update date Aug 29, 2019
Contact name Xin Sheng
Organization name University of Pennsylvania
Lab Susztak lab
Street address 3400 CCB
City Philadelphia
ZIP/Postal code 19104
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (6)
GSM3980308 RNAseq-Tfamf/f-12W-1
GSM3980309 RNAseq-Tfamf/f-12W-2
GSM3980310 RNAseq-Tfamf/f-12W-3
BioProject PRJNA556870
SRA SRP216519

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
GSE134950_RAW.tar 2.7 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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