Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Erythropoietin Receptor/β Common Receptor: A Shining Light on Acute Kidney Injury Induced by Ischemia-Reperfusion.

ABSTRACT: Acute kidney injury (AKI) is a health problem worldwide, but there is a lack of early diagnostic biomarkers and target-specific treatments. Ischemia-reperfusion (IR), a major cause of AKI, not only induces kidney injury, but also stimulates the self-defense system including innate immune responses to limit injury. One of these responses is the production of erythropoietin (EPO) by adjacent normal tissue, which is simultaneously triggered, but behind the action of its receptors, either by the homodimer EPO receptor (EPOR)₂ mainly involved in erythropoiesis or the heterodimer EPOR/β common receptor (EPOR/βcR) which has a broad range of biological protections. EPOR/βcR is expressed in several cell types including tubular epithelial cells at low levels or absent in normal kidneys, but is swiftly upregulated by hypoxia and inflammation and also translocated to cellular membrane post IR. EPOR/βcR mediates anti-apoptosis, anti-inflammation, pro-regeneration, and remodeling via the PI3K/Akt, STAT3, and MAPK signaling pathways in AKI. However, the precise roles of EPOR/βcR in the pathogenesis and progression of AKI have not been well defined, and its potential as an earlier biomarker for AKI diagnosis and monitoring repair or chronic progression requires further investigation. Here, we review biological functions and mechanistic signaling pathways of EPOR/βcR in AKI, and discuss its potential clinical applications as a biomarker for effective diagnosis and predicting prognosis, as well as directing cell target drug delivery.

SUBMITTER: Wu Y

PROVIDER: S-EPMC8278521 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury.

Project description:Kidney ischemia-reperfusion (I/R) injury is a common cause of acute kidney injury. We tested whether dexmedetomidine (Dex), an alpha2 adrenoceptor (α2-AR) agonist, protects against kidney I/R injury. Sprague-Dawley rats were divided into four groups: (1) Sham-operated group; (2) I/R group (40 min ischemia followed by 24 h reperfusion); (3) I/R group + Dex (1 μg/kg i.v. 60 min before the surgery), (4) I/R group + Dex (10 μg/kg). The effects of Dex postconditiong (Dex 1 or 10 μg/kg i.v. after reperfusion) as well as the effects of peripheral α2-AR agonism with fadolmidine were also examined. Hemodynamic effects were monitored, renal function measured, and acute tubular damage along with monocyte/macrophage infiltration scored. Kidney protein kinase B, toll like receptor 4, light chain 3B, p38 mitogen-activated protein kinase (p38 MAPK), sirtuin 1, adenosine monophosphate kinase (AMPK), and endothelial nitric oxide synthase (eNOS) expressions were measured, and kidney transciptome profiles analyzed. Dex preconditioning, but not postconditioning, attenuated I/R injury-induced renal dysfunction, acute tubular necrosis and inflammatory response. Neither pre- nor postconditioning with fadolmidine protected kidneys. Dex decreased blood pressure more than fadolmidine, ameliorated I/R-induced impairment of autophagy and increased renal p38 and eNOS expressions. Dex downregulated 245 and upregulated 61 genes representing 17 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, in particular, integrin pathway and CD44. Ingenuity analysis revealed inhibition of Rac and nuclear factor (erythroid-derived 2)-like 2 pathways, whereas aryl hydrocarbon receptor (AHR) pathway was activated. Dex preconditioning ameliorates kidney I/R injury and inflammatory response, at least in part, through p38-CD44-pathway and possibly also through ischemic preconditioning.

| S-EPMC4186414 | biostudies-literature

Murine Kidney cells: Control versus Ischemia reperfusion injury

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

A nonerythropoietic derivative of erythropoietin protects the myocardium from ischemia-reperfusion injury.

Project description:The cytokine erythropoietin (EPO) protects the heart from ischemic injury, in part by preventing apoptosis. However, EPO administration can also raise the hemoglobin concentration, which, by increasing oxygen delivery, confounds assignment of cause and effect. The availability of EPO analogs that do not bind to the dimeric EPO receptor and lack erythropoietic activity, e.g., carbamylated EPO (CEPO), provides an opportunity to determine whether EPO possesses direct cardioprotective activity. In vivo, cardiomyocyte loss after experimental myocardial infarction (MI) of rats (40 min of occlusion with reperfusion) was reduced from approximately 57% in MI-control to approximately 45% in animals that were administered CEPO daily for 1 week (50 microg/kg of body weight s.c.) with the first dose administered intravenously 5 min before reperfusion. CEPO did not increase the hematocrit, yet it prevented increases in left ventricular (LV) end-diastolic pressure, reduced LV wall stress in systole and diastole, and improved LV response to dobutamine infusion compared with vehicle-treated animals. In agreement with the cardioprotective effect observed in vivo, staurosporine-induced apoptosis of adult rat or mouse cardiomyocytes in vitro was also significantly attenuated ( approximately 35%) by CEPO, which is comparable with the effect of EPO. These data indicate that prevention of cardiomyocyte apoptosis, in the absence of an increase in hemoglobin concentration, explains EPO's cardioprotection. Nonerythropoietic derivatives such as CEPO, devoid of the undesirable effects of EPO, e.g., thrombogenesis, could represent safer and more effective alternatives for treatment of cardiovascular diseases, such as MI and heart failure. Furthermore, these findings expand the activity spectrum of CEPO to tissues outside the nervous system.

| S-EPMC548534 | biostudies-literature

Mouse kidney ischemia-reperfusion injury time course

Project description:Time course experiments involving bilateral renal ischemia reperfusion injury (IRI) in C57BL/6J mice (0 hr control, 20 min bilateral ischemia without reperfusion, 4, 16, 24, 36, 48, and 72 hrs post IRI). This dataset also includes IRI at 48 hrs and 72 hrs in Azin1 A-to-I locked and Azin1 A-to-I uneditable mice.

2024-09-30 | GSE267650 | GEO

Activation of the calcium-sensing receptor before renal ischemia/reperfusion exacerbates kidney injury.

Project description:Activation of the calcium-sensing receptor (CaSR) by ischemia/reperfusion (I/R) favours apoptosis in cardiomyocytes, hepatocytes and neurons. Its role in renal I/R is unknown. We investigated the impact of pharmacological preactivation of the CaSR on kidney structure and function in a murine model of bilateral renal 30-min ischemia and 48-hour reperfusion, and in a 6-year cohort of kidney transplant recipients (KTR). C57BL/6J mice were administered daily with CaSR agonist, R-568, or with vehicle for 48 hours. Evaluation of serum urea and creatinine levels, renal histology and urine metabolome by nuclear magnetic resonance showed that R-568 was not nephrotoxic per se. Following I/R, serum urea and creatinine levels increased higher in R-568-treated animals than in controls. Jablonski's score was significantly greater in R-568-treated kidneys, which showed a higher rate of cell proliferation and apoptosis in comparison to controls. Next, we retrospectively identified 36 patients (10.7% of our cohort) who were treated by CaSR agonist, cinacalcet, at the time of kidney transplantation (KTx). After matching these to 61 KTR upon type of donor, cold ischemic time, residual diuresis, and donor age, we observed that delayed graft function, i.e. need for dialysis in the first week after KTx, occurred in 42 and 23% of cinacalcet-treated and control groups, respectively (p?0.05). These data suggest that pharmacological preactivation of the CaSR before renal I/R exacerbates kidney injury.

| S-EPMC4346530 | biostudies-literature

Dynamics of necroptosis in kidney ischemia-reperfusion injury.

Project description:Necroptosis, a pathway of regulated necrosis, involves recruitment and activation of RIPK1, RIPK3 and MLKL, leading to cell membrane rupture, cell death and release of intracellular contents causing further injury and inflammation. Necroptosis is believed to play an important role in the pathogenesis of kidney ischemia-reperfusion injury (IRI). However, the dynamics of necroptosis in kidney IRI is poorly understood, in part due to difficulties in detecting phosphorylated MLKL (pMLKL), the executioner of the necroptosis pathway. Here, we investigated the temporal and spatial activation of necroptosis in a mouse model of unilateral warm kidney IRI, using a robust method to stain pMLKL. We identified the period 3-12 hrs after reperfusion as a critical phase for the activation of necroptosis in proximal tubular cells. After 12 hrs, the predominant pattern of pMLKL staining shifted from cytoplasmic to membrane, indicating progression to the terminal phase of necroptotic cell death. Mlkl-ko mice exhibited reduced kidney inflammation at 12 hrs and lower serum creatinine and tubular injury at 24 hrs compared to wild-type littermates. Interestingly, we observed increased apoptosis in the injured kidneys of Mlkl-ko mice, suggesting a relationship between necroptosis and apoptosis in kidney IRI. Together, our findings confirm the role of necroptosis and necroinflammation in kidney IRI, and identify the first 3 hrs following reperfusion as a potential window for targeted treatments.

| S-EPMC10652410 | biostudies-literature

Acute kidney injury after hepatic ischemia and reperfusion injury in mice.

Project description:Hepatic ischemia reperfusion (IR) is the leading cause of acute liver failure (ALF) during the perioperative period and patients with ALF frequently develop acute kidney injury (AKI). There is no effective therapy for AKI associated with ALF because pathomechanisms are incompletely characterized, in part due to the lack of an animal model. In this study, we characterize a novel murine model of AKI following hepatic IR. Mice subjected to approximately 70% liver IR not only developed acute liver dysfunction, but also developed severe AKI 24 h after liver injury. Mice subjected to liver IR developed histological changes of acute tubular injury including focal proximal tubular cell necrosis involving the S3 segment, cortical tubular ectasia, focal tubular simplification and granular bile/heme cast formation. In addition, there was focal interstitial edema and hyperplasia of the juxtaglomerular apparatus. Inflammatory changes in the kidney after hepatic IR included neutrophil infiltration of the interstitium and upregulation of several proinflammatory mRNAs (tumor necrosis factor-alpha, keratinocyte-derived cytokine, monocyte chemotactic protein-1, macrophage inflammatory protein-2, intercellular adhesion molecule-1). In addition, marked renal endothelial cell apoptosis was detected involving peritubular interstitial capillaries, accompanied by increased renal vascular permeability. Finally, there was severe disruption of renal proximal tubule epithelial filamentous-actin. Our results show that AKI rapidly and reproducibly develops in mice after hepatic IR and is characterized by renal tubular necrosis, inflammatory changes and interstitial capillary endothelial apoptosis. Our murine model of AKI after liver injury closely mimics human AKI associated with ALF and may be useful in delineating the mechanisms and potential therapies for this common clinical condition.

| S-EPMC2632727 | biostudies-literature

Murine Kidney cells: Control versus Ischemia reperfusion injury

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.

2011-08-01 | GSE29495 | GEO

Meclizine Preconditioning Protects the Kidney Against Ischemia-Reperfusion Injury.

Project description:Global or local ischemia contributes to the pathogenesis of acute kidney injury (AKI). Currently there are no specific therapies to prevent AKI. Potentiation of glycolytic metabolism and attenuation of mitochondrial respiration may decrease cell injury and reduce reactive oxygen species generation from the mitochondria. Meclizine, an over-the-counter anti-nausea and -dizziness drug, was identified in a 'nutrient-sensitized' chemical screen. Pretreatment with 100 mg/kg of meclizine, 17 h prior to ischemia protected mice from IRI. Serum creatinine levels at 24 h after IRI were 0.13 ± 0.06 mg/dl (sham, n = 3), 1.59 ± 0.10 mg/dl (vehicle, n = 8) and 0.89 ± 0.11 mg/dl (meclizine, n = 8). Kidney injury was significantly decreased in meclizine treated mice compared with vehicle group (p < 0.001). Protection was also seen when meclizine was administered 24 h prior to ischemia. Meclizine reduced inflammation, mitochondrial oxygen consumption, oxidative stress, mitochondrial fragmentation, and tubular injury. Meclizine preconditioned kidney tubular epithelial cells, exposed to blockade of glycolytic and oxidative metabolism with 2-deoxyglucose and NaCN, had reduced LDH and cytochrome c release. Meclizine upregulated glycolysis in glucose-containing media and reduced cellular ATP levels in galactose-containing media. Meclizine inhibited the Kennedy pathway and caused rapid accumulation of phosphoethanolamine. Phosphoethanolamine recapitulated meclizine-induced protection both in vitro and in vivo.

| S-EPMC4588407 | biostudies-literature

Effect of NAD+ boosting on kidney ischemia-reperfusion injury.

Project description:Acute kidney injury (AKI) is associated with a very high mortality and an increased risk for progression to chronic kidney disease (CKD). Ischemia-reperfusion injury (IRI) is a model for AKI, which results in tubular damage, dysfunction of the mitochondria and autophagy, and in decreased cellular nicotinamide adenine dinucleotide (NAD+) with progressing fibrosis resulting in CKD. NAD+ is a co-enzyme for several proteins, including the NAD+ dependent sirtuins. NAD+ augmentation, e.g. by use of its precursor nicotinamide riboside (NR), improves mitochondrial homeostasis and organismal metabolism in many species. In the present investigation the effects of prophylactic administration of NR on IRI-induced AKI were studied in the rat. Bilateral IRI reduced kidney tissue NAD+, caused tubular damage, reduced α-Klotho (klotho), and altered autophagy flux. AKI initiated progression to CKD, as shown by induced profibrotic Periostin (postn) and Inhibin subunit beta-A, (activin A / Inhba), both 24 hours and 14 days after surgery. NR restored tissue NAD+ to that of the sham group, increased autophagy (reduced p62) and sirtuin1 (Sirt1) but did not ameliorate renal tubular damage and profibrotic genes in the 24 hours and 14 days IRI models. AKI induced NAD+ depletion and impaired autophagy, while augmentation of NAD+ by NR restored tissue NAD+ and increased autophagy, possibly serving as a protective response. However, prophylactic administration of NR did not ameliorate tubular damage of the IRI rats nor rescued the initiation of fibrosis in the long-term AKI to CKD model, which is a pivotal event in CKD pathogenesis.

| S-EPMC8168908 | biostudies-literature

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