Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PCK1 loss contributes to kidney disease progression by altering mitochondrial fitness through its cataplerotic function [snRNA-seq_PCK1KI]

ABSTRACT: Metabolic alterations are recognized as key features of kidney injury, but their causal role in kidney repair remains a topic of debate. We investigate the role of PCK1, an enzyme involved in gluconeogenesis and cataplerosis, i.e. the removal of TCA intermediates from the mitochondrial matrix, in kidney disease. We demonstrate that PCK1 loss leads to injured mitochondria with decreased respiration and TCA metabolites accumulation. This results in inflammation, tubular injury and impaired tubule repair. We show that maintaining PCK1 expression in models of acute and chronic kidney disease preserves renal structure and function by improving TCA metabolite clearance. Restoration of PCK1 enhances mitochondrial health, reducing the progression to fibrosis. In humans, we confirm the correlation between PCK1 loss, mitochondrial injury as well as a failed tubule repair phenotype. We further observe the accumulation of TCA metabolites consistent with disrupted cataplerosis in chronic kidney disease. Our findings establish the maintenance of cataplerosis as an important factor of tubular physiology and repair and PCK1 as causal and potential therapeutic targets in this process.

ORGANISM(S): Mus musculus

PROVIDER: GSE280118 | GEO | 2025/06/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

PCK1 loss contributes to kidney disease progression by altering mitochondrial fitness through its cataplerotic function [snRNA-seq_Human]

Project description:Metabolic alterations are recognized as key features of kidney injury, but their causal role in kidney repair remains a topic of debate. We investigate the role of PCK1, an enzyme involved in gluconeogenesis and cataplerosis, i.e. the removal of TCA intermediates from the mitochondrial matrix, in kidney disease. We demonstrate that PCK1 loss leads to injured mitochondria with decreased respiration and TCA metabolites accumulation. This results in inflammation, tubular injury and impaired tubule repair. We show that maintaining PCK1 expression in models of acute and chronic kidney disease preserves renal structure and function by improving TCA metabolite clearance. Restoration of PCK1 enhances mitochondrial health, reducing the progression to fibrosis. In humans, we confirm the correlation between PCK1 loss, mitochondrial injury as well as a failed tubule repair phenotype. We further observe the accumulation of TCA metabolites consistent with disrupted cataplerosis in chronic kidney disease. Our findings establish the maintenance of cataplerosis as an important factor of tubular physiology and repair and PCK1 as causal and potential therapeutic targets in this process.

2025-06-18 | GSE280120 | GEO

PCK1 loss contributes to kidney disease progression by altering mitochondrial fitness through its cataplerotic function [snRNA-seq_PCK1KO]

2025-06-18 | GSE280119 | GEO

Immune-mediated Tubule Atrophy Promotes Acute Kidney Injury to Chronic Kidney Disease Transition

Project description:Incomplete repair after acute kidney injury (AKI) is associated with progressive loss of tubular cell function and development of chronic kidney disease (CKD). Here, we compared the kidney single-cell transcriptomes from the mice subjected to either unilateral ischemia-reperfusion kidney injury with contralateral nephrectomy (IRI/CL-NX, in which tubule repair predominates) or unilateral IRI with contralateral kidney intact (U-IRI, in which fibrosis and atrophy predominates) to investigate the mechanism(s) underlying transition to CKD following AKI.

2022-06-30 | GSE197626 | GEO

Inhibition of prolyl hydroxylase promotes the reprogramming of Sox9+ renal progenitor cells and renal regeneration

Project description:Mammalian kidney has very limited ability to repair or regenerate after acute kidney injury (AKI). The maladaptive repair of AKI promotes the progression to chronic kidney disease (CKD). Therefore, it is extremely urgent to explore new strategies to promote the repair/regeneration of injured renal tubules after AKI. It has been shown that hypoxia induces heart regeneration in adult mice. However, it is unknown whether hypoxia can induce kidney regeneration after AKI. In this study, we used a prolyl hydroxylase domain inhibitor (PHDI), MK-8617, to mimic hypoxia condition and found that MK-8617 significantly ameliorates ischemia reperfusion injury (IRI) induced acute kidney injury. We then showed that MK-8617 dramatically facilitates renal regeneration via promoting the proliferation of injured renal proximal tubular cells (RPTCs) after IRI-induced AKI. We then performed bulk mRNA sequencing and discovered that multiple nephrogenesis- related genes were significantly upregulated with MK-8617 pretreatment. Furthermore, we showed that MK-8617 may alleviate proximal tubule injury via stabilizing HIF-1α protein specifically in renal proximal tubular cells. We also demonstrated that MK-8617 promotes the reprogramming of renal proximal tubular cells to Sox9+ renal progenitor cells, and the regeneration of renal proximal tubules. In summary, we discovered that inhibition of prolyl hydroxylase improves renal proximal tubule regeneration after IRI-induced AKI via promoting the reprogramming of renal proximal tubular cells to Sox9+ renal progenitor cells.

2024-10-10 | GSE247560 | GEO

Injured tubular epithelia-derived CCN1 promotes the mobilization of fibroblasts toward the injury sites in acute kidney injury

Project description:Humoral factors that prompt fibroblasts to migrate to an injury site at an appropriate time point are deemed indispensable for repair after kidney injury. We herein demonstrated the pivotal roles for of injured tubule-derived Cellular Communication Network Factor 1 (CCN1) in the mobilization of fibroblasts to the injury site after kidney injury. Based on analyses of ligand-receptor interactions in vitro and tubular epithelial-specific transcriptomics in vivo, we identified the up-regulation of CCN1 during the early phases of kidney injury. CCN1 promotes fibroblast chemotaxis through focal adhesion kinase-ERK signaling. In vivo analyses utilizing tubular-specific CCN1 knockout mice demonstrated the sparse accumulation of fibroblasts around injured sites after injury, resulting that tissue fibrosis was ameliorated in CCN1-KO mice. These results reveal an epithelial - fibroblast CCN1 signaling axis that mobilizes fibroblasts to injured tubule early after acute injury but that promotes interstitial fibrosis at late timepoints.

2025-03-03 | GSE248209 | GEO

Transcriptional profiling of mouse proximal tubular epithelial cells during injury and repair

Project description:Proximal tubule has a remarkable capacity for repair after acute kidney injury. Whether dedifferentiation or a fixed progenitor population is responsible for this repair remains the subject of ongoing controversy. We have generated a novel genetic mouse model to address this question. We generated a Kim-1-GFPCreERt2 knockin mouse line (Kim1GCE) by homologous recombination. Kim-1 is expressed exclusively in dedifferentiated proximal tubule cells. We crossed this mouse line to the EGFP-L10a mouse line to perform Translating Ribosome Affinity Purification coupled with next generation sequencing (TRAP-seq) to identify the transcriptional signature of tubular epithelial cells during the course of injury and repair. TRAP-seq was performed in kidney samples at day 2, 7, and 14 after bilateral ischemia reperfusion injury and sham.

2019-11-29 | GSE121191 | GEO

Single cell profiling in COVID-19 associated acute kidney injury reveals patterns of tubule injury and repair in human

Project description:The cellular mechanisms of kidney tubule repair are poorly characterized in human. Here, we applied single-cell RNA sequencing to analyze the kidney in the first days after acute injury in 5 patients with severe COVID19. We found that tubule repair follows two converging patterns involving the plasticity of mature tubule cells and the expansion and differentiation of progenitor-like cells. Tubule repair by cell plasticity displayed substantial similarities between mouse and man and determined the transient expansion of undifferentiated tubule cells with altered functional and metabolic properties. Progenitor-like cells marked by PROM1 proliferated in response to injury and followed a differentiation process characterized by the sequential activation of the WNT, NOTCH and HIPPO signaling pathways. Taken together, our analyses reveal cell state transitions and fundamental cellular hierarchies underlying kidney injury and repair in patients.

2024-01-30 | GSE185778 | GEO

miRNA profiles of tubular cells (Rodent A and Rodent B)

Project description:MicroRNAs (miRNAs) are endogenous small RNAs of 18–23 nucleotides that regulate gene expression. Recently, plasma miRNAs have been investigated as biomarkers for various diseases. In the present study, we assessed whether the miRNA expression profiles of tubular tissues could discriminate proximal tubule injury and diagnose acute kidney injury (AKI) and the renal tubular dysfunction without morphological changes.

2015-03-17 | GSE66195 | GEO

miRNA profiles of tubular cells

2015-03-17 | GSE66134 | GEO

VCAM-1 mediates proximal tubule-immune cell cross talk in failed tubule recovery during AKI-to-CKD transition

Project description:Studies in animal models have suggested a linkage between the inflammatory response to injury and subsequent nephron loss during the acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Failure of normal repair during the CKD transition correlates with de novo expression of vascular cell adhesion protein-1 (VCAM-1) by a subset of injured proximal tubule cells. This study identified the role of VCAM-1 expression in promoting the failed repair state. Single-cell transcriptome analysis of patients with AKI and CKD and whole kidney RNA and protein analyses of mouse models of CKD confirmed a marked increase of VCAM-1 expression in the proximal tubules of injured kidneys. In immortalized mouse proximal tubular cells and primary cultured renal cells (PCRCs), VCAM-1 expression was induced by proinflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-1β. Analyses of bulk RNA sequencing of TNF-α-treated primary cultured renal cells or pseudo-bulk RNA sequencing of biopsies from Kidney Precision Medicine Project datasets indicated activation of NF-κB and an enrichment of inflammatory response and cell adhesion pathways in VCAM-1-positive cells. Pharmacological inhibition of NF-κB signaling or genetic deletion of myeloid differentiation factor 88 and TIR domain-containing adapter-inducing interferon-β suppressed TNF-α- and IL-1β-induced VCAM-1 expression in vitro. TNF-α stimulation or overexpression of VCAM-1 significantly increased splenocyte adhesion to the mouse proximal tubular monolayer in culture. These results demonstrate that persistence of proinflammatory cytokines after AKI can induce NF-κB-dependent VCAM-1 expression by proximal tubule cells, mediating increased immune cell adhesion to the tubule and thus promoting further tubule injury and greater risk of progression from AKI to CKD.

2024-09-03 | GSE254359 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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