Cell-Specific Image-guided Transcriptomics of Ischemic Acute Kidney Injury
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA550256 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9586740_1.fastq.gz | Fastqsanger.gz | |||
| SRR9586740_2.fastq.gz | Fastqsanger.gz | |||
| SRR9586741_1.fastq.gz | Fastqsanger.gz | |||
| SRR9586741_2.fastq.gz | Fastqsanger.gz | |||
| SRR9586742_1.fastq.gz | Fastqsanger.gz |
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Project description:The highly heterogeneous nature of the kidney's tubular epithelium has made it challenging to identify unique, cell-specific pathways particularly when renal injury causes the loss of fiduciary landmarks. Here, we combine a cell-specific luciferase reporter system with a chemo-selective substrate to identify specific Òat riskÓ tissues. We demonstrate that this platform system has the power to identify both cell-specific pathophysiological events and cell-specific transcriptional changes and consequently can identify novel therapeutic targets. Using the kidney ischemia-reperfusion model (iAKI), we found that lipid peroxidation mirrored H2O2 generation but with entirely different timing and sensitivity to ischemia depending on the nephron segment. We found the collecting duct demonstrated intensive ROS generation and transcriptional analysis demonstrated mitochondrial distress. In fact, pretreatment with a single bolus of a mitochondrial antioxidant, MitoTEMPO delayed ROS generation and significantly reduced acute oxidative stress associated injury. These data demonstrate that iAKI differentially targets different nephron segments, demonstrating the complexity of kidney injury includes multiple segments. Our in vivo ROS detection system can explore complex injuries in heterogeneous organs by leveraging image guidance for tissue interrogation.
2019-06-24 | GSE133184 | GEO
Project description:The kidney's inherent complexity has made identifying cell-specific pathways challenging, particularly when temporally associating them with the dynamic pathophysiology of acute kidney injury (AKI). Here, we combine renal cell-specific luciferase reporter mice using a chemoselective luciferin to guide the acquisition of cell-specific transcriptional changes in C57BL/6 background mice. Hydrogen peroxide generation, a common mechanism of tissue damage, was tracked using a peroxy-caged-luciferin to identify optimum time points for immunoprecipitation of labeled ribosomes for RNA-sequencing. Together, these tools revealed a profound impact of AKI on mitochondrial pathways in the collecting duct. In fact, targeting the mitochondria with an antioxidant, ameliorated not only hydrogen peroxide generation, but also significantly reduced oxidative stress and the expression of the AKI biomarker, LCN2. This integrative approach of coupling physiological imaging with transcriptomics and drug testing revealed how the collecting duct responds to AKI and opens new venues for cell-specific predictive monitoring and treatment.
| S-EPMC6718519 | biostudies-literature
Project description:Ischemic preconditioning is effective in limiting subsequent ischemic acute kidney injury in experimental models. microRNAs are an important class of post-transcriptional regulator and show promise as biomarkers of kidney injury. An evaluation was performed of the time- and dose-dependent effects of ischemic preconditioning in a rat model of functional (bilateral) ischemia-reperfusion injury. A short, repetitive sequence of ischemic preconditioning resulted in optimal protection from subsequent ischemia-reperfusion injury. A detailed characterization of microRNA expression in ischemic preconditioning/ischemia-reperfusion injury was performed by small RNA-Seq.
2021-12-31 | E-MTAB-9896 | biostudies-arrayexpress
Project description:Ischemic preconditioning is effective in limiting subsequent ischemic acute kidney injury in experimental models. microRNAs are an important class of post-transcriptional regulator and show promise as biomarkers of kidney injury. An evaluation was performed of the time- and dose-dependent effects of ischemic preconditioning in a rat model of functional (bilateral) ischemia-reperfusion injury. A short, repetitive sequence of ischemic preconditioning resulted in optimal protection from subsequent ischemia-reperfusion injury. A detailed characterization of microRNA expression in ischemic preconditioning/ischemia-reperfusion injury was performed by Exiqon miRCURY microRNA array.
2021-12-31 | E-MTAB-9900 | biostudies-arrayexpress
Project description:Effect of tubular IKKb deletion in acute ischemic kidney injury
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Project description:Female sex protects against development of acute kidney injury (AKI). While sex hormones may be involved in protection, the role of differential gene expression is unknown. We conducted gene profiling in male and female mice with or without kidney ischemia-reperfusion injury. Mice underwent bilateral renal pedicle clamping (30 min), and tissues were collected 24 hours after reperfusion. RNA-sequencing was performed on proximal tubules and kidney endothelial cells. Female mice were resistant to ischemic injury compared to males, determined by plasma creatinine, histologic scores, neutrophil infiltration, and extent of apoptosis. Sham mice had sex-specific gene disparities in proximal tubule and endothelium, and male mice showed profound gene dysregulation with ischemia-reperfusion compared to females. After ischemia proximal tubules from females exhibited smaller increases compared to males in injury-associated genes Lcn2, Havcr1, and Krt18, and no upregulation of Sox9 or Krt20. Endothelial upregulation of adhesion molecules and cytokines/chemokines occurred in males, but not females. Upregulated genes in male ischemic proximal tubules were linked to tumor necrosis factor and Toll-like receptor pathways, while female ischemic proximal tubules showed upregulated genes in pathways related to transport. The data suggest that sex-specific gene expression profiles in male and female proximal tubule and endothelium may underlie disparities in susceptibility to AKI.
2020-09-09 | GSE144622 | GEO
Project description:Background: Acute kidney injury (AKI) is a common clinical event with high morbidity and mortality. We previously demonstrated that injection of cord blood endothelial colony forming cell (ECFC)-derived exosomes, highly enriched in miRNA(miR)-486-5p, prevented ischemic kidney injury in mice. While preclinical models support involvement of several miRs in AKI, the direct effects of miR-486-5p on injury and the kidney transcriptome are unknown. Objective: We studied effects of miR-486-5p in mice with kidney ischemia-reperfusion (IR) injury, and compared the impact of miR-486-5p and ECFC-derived exosomes on the transcriptome of proximal tubules (PTs) and renal endothelial cells. Methods: Adult male mice were subjected to bilateral kidney ischemia (30 min), and injected via tail vein with or without vehicle, miR-486-5p mimic, ECFC-derived exosomes, or scramble miR at the start of reperfusion. Plasma and tissues were collected 24 hrs after reperfusion, and proximal tubular and endothelial cells were isolated for mRNA analysis by RNA-Seq. Results: In mice with kidney IR, injection of miR-486-5p mimic increased levels of miR-486-5p in proximal tubules and endothelial cells, and significantly improved plasma creatinine, histological injury, neutrophil infiltration, and apoptosis, compared to vehicle treatment. MiR-486-5p inhibited expression of phosphatase and tensin homolog (PTEN), and activated AKT. Similar results were observed with exosomes, but scramble miR had no effect. In proximal tubules, miR-486-5p or exosomes reduced expression of several AKI genes (e.g. Lcn2, Havcr1 and Krt20) and caused alterations in apoptotic genes compared to IR alone. In endothelium, miR-486-5p or exosomes caused milder effect than in PTs but still impacting on expression of injury-related genes. Conclusion: MiR-486-5p protects mice against ischemic kidney injury. Both miR-486-5p and exosomes reduce expression of apoptotic genes in PTs and endothelium. The results suggest that systemic delivery of miR-486-5p has therapeutic potential in ischemic AKI.
2023-10-10 | GSE159701 | GEO
Project description:We have performed NGS-derived transcriptome profiling (RNA-seq) to examine the impact of hypoxic preconditioning in post-ischemic kidney injury. Experimental set up: 4 C57BL/6J (male, 8 wks of age) mice were subjected to hypoxia (8%O2) for 48hrs and then subjected to unilateral renal ischemic reperfusion mice (IRI). 4 normoxic littermates subjected to renal IRI served as controls. Injured kidneys were harvested at day 3 following renal IRI and were subjected to NGS. Methods: Poly(A) RNA sequencing library was prepared following Illumina’s TruSeq-stranded-mRNA sample preparation protocol. Quality control analysis and quantification of the sequencing library were performed using Agilent Technologies 2100 Bioanalyzer High Sensitivity DNA Chip. Paired-ended sequencing was performed on Illumina’s NovaSeq 6000 sequencing system.
2021-07-19 | GSE156516 | GEO
Project description:Aging is associated with an increased incidence and severity of acute renal failure. However, the molecular mechanism(s) underlying the increased susceptibility to injury remain undefined. These experiments were designed to investigate the influence of age on the response of the kidney to ischemic and nephrotoxic challenge. Renal slices were prepared from young (4 month), aged ad libitum (aged-AL; 24 month) and aged caloric restricted (aged-CR; 24 month) male Fischer 344 rats and subjected to ischemic stress (anoxia, 100% N2) for 0-60 min and to cisplatin (2 mM, 4hr) challenge. As assessed by biochemical and histological evaluation, slices from aged-AL rats were more susceptible to injury than young counterparts. Importantly, caloric restriction attenuated the increased susceptibility to injury. In an attempt to identify the molecular pathway(s) underlying this response, microarray analysis was performed on tissue harvested from the same animals used for the functional analysis. RNA was isolated and the corresponding cDNA was hybridized to CodeLink™ Rat Whole Genome Bioarray slides. Subsequent gene expression analysis was performed using GeneSpring software. Using two-sample t-tests and a 2-fold cut-off, the expression of 92 genes was changed during aging and attenuated by caloric restriction. In summary, several changes were identified that may be associated with the increased susceptibility of aging kidney to injury. Keywords: aging, caloric-restriction, kidney
2007-08-30 | GSE6110 | GEO
Project description:miRNA profiling of kidney tissue from C57BL/6 mice that received a 30 minute ischemic injury compared with control kidney tissue from mice that received sham operation only. Two condition experiment - sham and ishemic injury (IRI). Eight time points were measured using pooled samples from three mice.
2011-07-31 | E-GEOD-29495 | biostudies-arrayexpress