Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hypothermic machine perfusion alleviates DCD graft liver injury by inducing the expression of KLF2 and promoting macrophage efferocytosis

ABSTRACT: This study aims to investigate the protective effects and underlying mechanisms of hypothermic machine perfusion (HMP) on ischemia-reperfusion injury (IRI) in liver grafts from donation after cardiac death (DCD), with a specific focus on the regulation of KLF2 expression and its role in modulating macrophage efferocytosis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE296118 | GEO | 2025/05/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Doxycycline alters porcine renal proteome and degradome during hypothermic machine perfusion

Project description:Ischemia/reperfusion injury (IRI) is a hallmark of tissue injury in donation after circulatory death (DCD) kidneys. The implementation of hypothermic machine perfusion (HMP) provides a platform for repair of DCD kidneys. Doxycycline administration has shown protective effects during IRI. Here, we explore the impact of doxycycline on proteolytic degradation mechanisms and the urinary proteome of perfused kidney grafts. Porcine kidneys underwent 30 min of warm ischemia, 24 h of oxygenated HMP (control/doxycycline) and 240 min of ex-vivo reperfusion. A high-efficiency undecanal-based N-termini enrichment workflow (HUNTER) was performed to identify the tissue degradome. In addition, a proteomic analysis was applied on urine samples collected during reperfusion using label-free quantitation (LFQ) mass spectrometry. Hierarchical clustering showed distinctive clustering profiles between urine samples collected at T15 min (metabolism) and T240 min (complement and coagulation). At T10, significantly more degraded proteins were observed in perfusates of the control group. At T240, significantly more degraded proteins were observed in the doxycycline group, indicating that doxycycline alters protein degradation during HMP. In conclusion, doxycycline administration during HMP led to significant proteomic differences including protective effects by attenuating urinary NGAL levels. Ultimately, we unravelled multiple pathways that undergo alterations during machine perfusion that can be targeted to attenuate IRI induced injury.

2022-08-12 | PXD029599 | Pride

Expression data from an ex vivo ischaemia reperfusion model of renal deceased by cardiac death (DCD) donation in rat

2012-03-22 | GSE36671 | GEO

Expression data from an ex vivo ischaemia reperfusion model of renal deceased by cardiac death (DCD) donation in rat

Project description:In DCD organ donation one of the significant problems for the organ is the inflammatory response due to ischaemia reperfusion injury caused by warm ischaemia prior to retrieval followed by warm reoxygenation upon transplantation. We developed a model where a DCD kidney was retrieved and preserved using hypothermic machine perfusion with cold University of Wisconsin solution with/without the addition of heparinoids low molecular weight heparin and pentosan polysulfate (PPS) followed by warm oxygenated perfusion with modified Krebs-Henseleit buffer to simulate early ischaemia reperfusion injury (IRI). The donor rats consisted of a control group cold perfusion group compared to warm perfusion and groups treated with either low molecular weight heparin or PPS to assess their activity in ameliorating IRI. We used equimolar pooled RNA samples from each group to perform an exploratory microarray experiment Donor kidneys were harvested and preserved by hypothermic machine perfusion with University of Wisconsin (UW) Solution for 3 hours followed by warm oxygenated perfusion with modified Krebs-Henseleit buffer for 30 minutes to simulate transplantation and whole blood ischaemia reperfusion injury. The model was then used to test the anti-inflammatory properties of the glycosaminoglycan heparin and PPS when used as supplements into perfusate solutions. Half of the donor kidney was used to extract RNA using the Tri reagent and stored in RNA Later. The qualitative best three RNAs from each group were quantified by fluorimetry and mixed in an equimolar manner and used for microarray analysis.

2012-03-22 | E-GEOD-36671 | biostudies-arrayexpress

The microRNA expression profile in donation after cardiac death (DCD) livers and its ability to identify primary non function

2015-04-09 | GSE67689 | GEO

PROTEOMIC ANALYSIS OF MACHINE PERFUSION SOLUTION FROM BRAIN DEAD DONOR KIDNEYS REVEALS THAT COMPLEMENT ACTIVATION IS ASSOCIATED WITH 1-YEAR OUTCOME

Project description:Current strategies to assess donor kidney quality are based on clinical scores or require biopsies for histological assessment. Non-invasive strategies to identify and predict graft outcome at an early stage are therefore needed. Our aim was to evaluate the secretome in non-oxygenated hypothermic machine perfusion (HMP) perfusate of donation after brain death (DBD) kidneys by comparing proteomic profiles of good outcome (GO) and ¬suboptimal outcome (SO) 1-year post transplantation. Samples taken 15 minutes after start of HMP (T1) and before termination of HMP (T2) were analysed using liquid chromatography tandem mass spectrometry (LC MS/MS). Hierarchical clustering of the 100 most abundant proteins showed discrimination between grafts with a GO and SO at T1. Upregulated expression of proteins involved in classical complement activation at both T1 and T2, and downregulated expression lipid metabolism at T1 and of cytoskeletal proteins at T2 in GO vs. SO was observed. ATP-citrate synthase and fatty acid binding protein 5 (T1) and immunoglobulin heavy variable 2-26 and Desmoplakin (T2) showed 91% and 86% predictive values respectively for transplant outcome. This study shows that the secretome of DBD kidneys can distinguish between outcome 1-year post transplantation. Furthermore, it provides insights into mechanisms that could play a role in post- transplant outcomes.

2022-08-12 | PXD027127 | Pride

The microRNA expression profile in donation after cardiac death (DCD) livers and its ability to identify primary non function

Project description:The microRNA expression profile in donation after cardiac death (DCD) livers its ability to identify primary non function DCD livers are a marginal organ and their usein transplantation is associated with a higher risk of primary non function (PNF), or early graft dysfunction (EGD). We compared a three groups of DCD livers defined as PNF (n=7) retransplanted within a week, good functional outcome (n=7) AST < 1000IU/L and EGD (n=9) AST>2500IU/L . RNA was extracted from archived histology samples and miRNA expression was analysed using the affymetrix Genechip miRNA 2.0 assays.

2015-04-09 | E-GEOD-67689 | biostudies-arrayexpress

Hypothermic oxygenated machine perfusion promotes mitophagy flux against hypoxia ischemic injury in donation after circulatory death liver

Project description:HOPE is a dynamic preservation method to attenuate IRI in DCD liver. In a rat model of DCD liver, the protective mechanism of HOPE is probably by promoting mitophagy flux in response to hypoxia-ischemic injury. We performed gene expression profiling analysis using data obtained from RNA-seq of 4 different groups in DCD liver.

2022-10-15 | GSE215134 | GEO

13C glucose labelling studies using 2D NMR is a useful tool for determining ex vivo whole organ metabolism during hypothermic machine perfusion of kidneys

Project description:Background: The aim of this study is to determine the feasibility of using Nuclear Magnetic Resonance (NMR) tracer studies (13C-enriched glucose) to detect ex vivo de novo metabolism in the perfusion fluid and cortical tissue of porcine kidneys during hypothermic machine perfusion (HMP). Methods: Porcine kidneys (n=6) were subjected to 24hrs of HMP using the Organ Recovery Systems LifePort Kidney perfusion device. Glucose, uniformly enriched with the stable isotope 13C ([U-13C] glucose) was incorporated into KPS-1-like perfusion fluid at a concentration of 10 mM. Analysis of perfusate was performed using both 1D 1H and 2D 1H,13C Heteronuclear single quantum coherence NMR spectroscopy (HSQC). The metabolic activity was then studied by quantifying the proportion of key metabolites containing 13C in both perfusate and tissue samples. Results: There was significant enrichment of 13C in a number of central metabolites present in both the perfusate and tissue extracts and was most pronounced for lactate and alanine. The total amount of enriched lactate (per sample) in perfusion fluid increased during HMP (31.1 ± 12.2 nmol at 6 hrs vs 93.4 ± 25.6 nmol at 24 hrs p<0.01). The total amount of enriched alanine increased in a similar fashion (1.73 ± 0.89 nmol at 6hrs vs 6.80 ± 2.56 nmol at 24hrs (p<0.05). In addition, small amounts of enriched acetate and glutamic acid was evident in some samples. Conclusions: This study conclusively demonstrates that de novo metabolism occurs during HMP and highlights active metabolic pathways in this hypothermic, hypoxic environment. While the majority of the 13C-enriched glucose is metabolised into glycolytic endpoint metabolites such as lactate, the presence of non-glycolytic pathway derivatives suggests that metabolism during HMP is more complex than previously thought. Isotopic labelled ex vivo organ perfusion studies using 2D-NMR are feasible and informative.

2017-10-16 | MTBLS367 | MetaboLights

Expression data from a model of renal deceased by cardiac death (DCD) donation in rat

Project description:In DCD organ donation one of the significant problems for the organ is the inflammatory response due to ischaemiua reperfusion injury caused by warm ischaemia prior to retrieval followed by warm reoxygenation upon transplantation. We developed a model where a DCD kidney was retrieved and stoired overnight then the organ was surgically attached to the femoral artery of a recipient rat and blood flow restored for up to six hours to simulate early ischaemia reperfusion injury (IRI). The recipient rats consisted of a control group compared to groups recieveing either low molecular weight heparin or an anti-inflammatory peptide to assess their activity in ameliorating IRI. We used equimolar pooled RNA samples from each group to perform an exploratory microarray experiment.

2012-02-06 | GSE35555 | GEO

Transcriptome Analysis of Kidney Grafts Subjected to Normothermic Ex-Vivo Kidney Perfusion

Project description:Normothermic ex-vivo kidney perfusion (NEVKP) has demonstrated superior outcomes for donation-after-cardiovascular death (DCD) grafts compared to static cold storage (SCS). To determine the mechanisms responsible for this, we performed an unbiased genome-wide microarray analysis. Kidneys from 30kg-Yorkshire pigs were subjected to 30min of warm ischemia followed by 8hrs of NEVKP or SCS, or no storage (NS), prior to auto-transplantation. mRNA expression was analyzed on POD3 renal biopsies.

2021-07-15 | GSE155418 | 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