Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney disease [miRNA-seq]

ABSTRACT: Chronic kidney disease (CKD) complicates cisplatin-based chemotherapy of cancer patients. Here we investigate microRNA (miRNA)-regulated transcriptomic activity to unveil biological processes associated with cisplatin-induced kidney injury. Implementing chimeric-eCLIP-seq approach to a mouse model for cisplatin-induced CKD, we identify direct pairs of miRNA and their target messenger RNA in the injured kidney. We find a dedicated transcriptomic program directed by a group of miRNAs that alter metabolic pathways centered on mitochondria in the injured kidneys. Specifically, cisplatin-induced miRNA, miR-429-3p suppresses the mitochondria pathway that catalyzes branched-chain amino acid (BCAA), eventually leading to lipid peroxidation-dependent cell death, called ferroptosis. Thus, the identification of miRNA-429-3p-mediated stimulation of ferroptosis suggests a therapeutic potential for BCAA pathway modulation in ameliorating CKD and cisplatin-associated nephrotoxicity.

ORGANISM(S): Mus musculus

PROVIDER: GSE242807 | GEO | 2023/11/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

MicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney disease [RNA-seq]

Project description:Chronic kidney disease (CKD) complicates cisplatin-based chemotherapy of cancer patients. Here we investigate microRNA (miRNA)-regulated transcriptomic activity to unveil biological processes associated with cisplatin-induced kidney injury. Implementing chimeric-eCLIP-seq approach to a mouse model for cisplatin-induced CKD, we identify direct pairs of miRNA and their target messenger RNA in the injured kidney. We find a dedicated transcriptomic program directed by a group of miRNAs that alter metabolic pathways centered on mitochondria in the injured kidneys. Specifically, cisplatin-induced miRNA, miR-429-3p suppresses the mitochondria pathway that catalyzes branched-chain amino acid (BCAA), eventually leading to lipid peroxidation-dependent cell death, called ferroptosis. Thus, the identification of miRNA-429-3p-mediated stimulation of ferroptosis suggests a therapeutic potential for BCAA pathway modulation in ameliorating CKD and cisplatin-associated nephrotoxicity.

2023-11-01 | GSE242808 | GEO

MicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney disease [CLIP-seq]

2023-11-01 | GSE242806 | GEO

Loss of proximal tubular Kruppel-like factor 6 (KLF6) is protective against AKI and CKD

Project description:Altered cellular metabolism in kidney proximal tubule (PT) cells plays a critical role in the development and progression of acute kidney injury (AKI). The transcription factor Krüppel-like factor 6 (KLF6) is rapidly and robustly induced in the PT after AKI, suggesting an early-inducible injury response gene. PT-specific Klf6 knockdown (Klf6PTKO) are protected from AKI and resulting fibrosis in mice. Combined RNA-sequencing and ChIP-sequencing demonstrated preserved expression of genes encoding branched chain amino acid (BCAA) catabolic enzymes in Klf6PTKO mice, with several of the genes also having KLF6 binding sites close to their transcription start sites. Conversely, inducible KLF6 overexpression suppressed expression of BCAA genes and exacerbated kidney injury and fibrosis in mice. Injured kidney cells could not respond to the BCAA catabolic activator BT2, and injured cells overexpressing KLF6 were less able to utilize BCAA. Thus, targeting KLF6-mediated suppression of BCAA catabolism may serve as key therapeutic target in AKI and kidney fibrosis.

2021-05-18 | GSE150656 | GEO

FXR protects cisplatin-induced AKI via transcriptional regulation of ferroptosis.

Project description:Farnesoid X receptor (FXR, also known as NR1H4) is crucial to nephroprotective in several kinds of kidney diseases, including obesity, diabetes, aging, acute kidney injury and chronic kidney disease. FXR plays a key role in maintaining cholesterol and bile acid levels and is highly expressed in the liver, intestine and kidneys. In kidney diseases, it is reported that FXR has anti-lipogenic, anti‐inflammatory, antifibrotic, and antioxidant functions. Here, using genomics analysis, we investigated whether FXR attenuates cisplatin-induced AKI through the regulation of ferroptosis. The increased blood urea nitrogen, serum creatinine and ferroptotic responses in cisplatin-induced AKI mice were attenuated by treatment with FXR agonist, GW4064, while those were exacerbated in FXR knockout mice. Using RNA-sequencing analysis, we found novel target genes for FXR associated with ferroptosis. FXR agonist treatment increases lipid and glutathione metabolic gene expression and decreases cell death genes expression. This study identifies transcriptional regulation of ferroptosis by FXR as a potential therapeutic target for cisplatin-induced AKI.

2022-07-06 | GSE193860 | GEO

Single-cell RNAseq analysis of kidneys from RNLS knockout mice with chronic kidney disease treated with RNLS peptide encapsulated in mesonanoparticles

Project description:We compared transcriptome profiles of kidneys from RNLS KO mice treated with RNLS peptide RP81 in mesonanoparticle (RP81-MNP) or with empty MNP (control). Our study provided some molecular mechanism of how RNLS peptide protected kidney from cisplatin-induced CKD.

2021-12-16 | GSE174010 | GEO

Single-cell RNAseq analysis of kidneys from Wild Type and RNLS knockout control mice and mice with chronic kidney disease

Project description:We compared transcriptome profiles of WT kidneys with that of RNLS KO kidneys. We also compared transcriptome profiles of healthy kidneys to CKD kidneys. Our study represents the first detailed transcriptome analysis of kidneys from mice with cisplatin-induced chronic kidney disease and provides the dissection of renalase functions.

2021-12-16 | GSE174013 | GEO

DNA-PKcs drives CKD progression by activating TAF7/RAPTOR/mTORC1 signaling-mediated metabolic reprogramming

Project description:<p>Kidney injury initiates epithelial dedifferentiation and myofibroblast activation during the progression of chronic kidney disease (CKD). Herein, we found that the expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) was significantly increased in the kidney tissues of both CKD patients and CKD mice induced by unilateral ureteral obstruction (UUO) and unilateral ischemia-reperfusion (UIR) injury. In vivo, knockout of DNA-PKcs or treatment with its specific inhibitor NU7441 hampered the development of CKD in mice. In vitro, DNA-PKcs deficiency preserved epithelial cell phenotype and inhibited fibroblast activation induced by transforming growth factor-beta 1 (TGF-beta-1). Additionally, our results showed that TBP-associated factor 7 (TAF7), as a possible substrate of DNA-PKcs, enhanced mTORC1 activation by upregulating RAPTOR expression, which subsequently promoted metabolic reprogramming in injured epithelial cells and myofibroblasts. Taken together, DNA-PKcs can be inhibited to correct metabolic reprogramming via the TAF7/mTORC1 signaling in CKD, and serve as a new target for treating CKD.</p>

2023-01-25 | MTBLS5971 | MetaboLights

TFEB-driven lysosomal biogenesis is pivotal for PGC1a-dependent renal stress resistance

Project description:Because injured mitochondria can accelerate cell death through the elaboration of oxidative free radicals and other mediators, it is somewhat paradoxical that proliferator gamma coactivator 1-alpha (PGC1a), a stimulator of increased mitochondrial abundance, protects stressed renal cells instead of potentiating injury. Here we report that PGC1a’s induction of lysosomes via transcription factor EB (TFEB) may be pivotal for kidney protection. CRISPR and stable gene transfer showed that PGC1a knockout tubular cells were sensitized to the genotoxic stressor cisplatin whereas transgenic cells were protected. The biosensor mtKeima unexpectedly revealed that cisplatin blunts mitophagy both in cells and mice. PGC1a not only counteracted this effect but also raised basal mitophagy, as did the downstream mediator nicotinamide adenine dinucleotide (NAD+). PGC1a did not consistent affect known autophagy pathways modulated by cisplatin. Instead RNA sequencing identified coordinated regulation of lysosomal biogenesis via TFEB. This effector pathway was sufficiently important that inhibition of TFEB or lysosomes unveiled a striking harmful effect of excess PGC1a in cells and conditional mice. These results uncover an unexpected effect of cisplatin on mitophagy and PGC1a’s exquisite reliance on lysosomes for kidney protection. Finally, the data illuminate TFEB as a novel target for renal tubular stress resistance.

2019-06-10 | GSE126259 | GEO

Signature analyses for circulating extracellular vesicle in chronic kidney disease

Project description:Chronic kidney disease (CKD) accelerates vascular calcification (VC) via phenotypic switching of vascular smooth muscle cells (VSMCs). We investigated the roles of circulating small extracellular vesicles (sEVs) between the kidneys and VSMCs and uncovered relevant sEV-propagated microRNAs (miRNAs) and their biological signaling pathways. We established CKD models in rats and mice by adenine-induced tubulointerstitial fibrosis. The miRNA transcriptome of sEVs revealed a depletion of several miRNAs in CKD. Their expression levels in sEVs from CKD patients were correlated to kidney function. This study revealed the transcriptomic landscape of miRNAs propagated in sEVs in CKD. We investigated the therapeutic potential of miRNAs in VC.

2022-12-31 | GSE217558 | GEO

Mitochondrial Proteomics in a murine model of CKD

Project description:This project involves TMT-labeled proteomics analysis of mitochondria isolated from skeletal muscle, heart, and kidney of mice with and without chronic kidney disease (CKD). CKD was induced by adenine-supplementation of the diet for 6 months. Mouse strain was C57BL6J mice from Jackson Lab, aged 6 months prior to start of the diet. Mitochondria were isolated from skeletal muscle, heart, and kidney and immediately snap frozen and stored at -80C until processing.

2021-10-06 | PXD021847 | JPOST Repository

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data