Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

NLRC5 deficiency protects against acute kidney injury in mice by mediating CEACAM1 signaling

ABSTRACT: Although there is significant progress in understanding the structure and function of NLRC5, a member of the NOD like receptor (NLR) family, in the context of MHC class I gene expression, the functions of NLRC5 in innate and adaptive immune responses beyond the regulation of MHC class I genes remain controversial and unresolved. In particular, the role of NLRC5 in the kidney keeps unknown. In this study, we found that NLRC5 was significantly upregulated in the kidney from mice with renal ischemia/reperfusion injury (IRI). NLRC5 deficient (NLRC5-/-) mice significantly ameliorated renal injury as evidenced by decreased serum creatinine levels, improved morphological injuries, and reduced inflammatory responses versus wild type mice. Similar protective effects were also observed in cisplatin-induced acute kidney injury (AKI). Mechanistically, NLRC5 contributed to renal injury by promoting tubular epithelial cell apoptosis and reducing inflammatory responses which is associated with, at least in part, the negative regulation of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). To determine the relative contribution of NLRC5 expression by parenchymal cells or leukocytes to renal damage during IRI, we generated bone marrow (BM) chimeric mice. NLRC5-/- mice engrafted with WT hematopoietic cells had significantly lower serum creatinine and less tubular damage than WT mice reconstituted with NLRC5-/- BM, suggesting that NLRC5 signaling in renal parenchymal cells plays the dominant role in mediating renal damage. Collectively, modulation of NLRC5-mediated pathway may have important therapeutic implications for patients with AKI.

ORGANISM(S): Mus musculus

PROVIDER: GSE109374 | GEO | 2018/01/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Tubular epithelial NF-κB activity regulates acute ischemic kideny injury [OTT-211009]

Project description:NF-κB is a key regulator of innate and adaptive immunity and is implicated in the pathogenesis of acute kidney injury (AKI). The cell type-specific functions of NF-κB in the kidney are unknown; however, the pathway serves distinct functions in immune and tissue-parenchymal cells. We analyzed tubular epithelial-specific NF-κB signaling in a mouse model of ischemia-reperfusion injury (IRI)-induced AKI. NF-κB reporter activity and nuclear localization of phosphorylated NF-κB subunit p65 analyses in mice revealed widespread NF-κB activation in renal tubular epithelia and in interstitial cells following IRI that peaked at 2-3 days after injury. To genetically antagonize tubular epithelial NF-κB activity, we generated mice expressing the human NF-κB super-repressor IκBα∆N in renal proximal, distal, and collecting duct epithelial cells. These mice were protected from IRI-induced AKI, as indicated by improved renal function, reduced tubular apoptosis, and attenuated neutrophil and macrophage infiltration. Tubular NF-κB-dependent gene expression profiles revealed temporally distinct functional gene clusters for apoptosis, chemotaxis, and morphogenesis. Primary proximal tubular cells isolated from IκBα∆N-expressing mice exposed to hypoxia-mimetic agent cobalt chloride were protected from apoptosis and expressed reduced levels of chemokines. Our results indicate that postischemic NF-κB activation in renal-tubular epithelia aggravates tubular injury and exacerbates a maladaptive inflammatory response.

2016-09-17 | GSE87024 | GEO

Tubular epithelial NF-κB activity regulates acute ischemic kideny injury [130402-EV-EmxdN]

2016-09-17 | GSE87023 | 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

Blockade of TNFα after ischemia reperfusion injury ameliorates renal prognosis

Project description:Recently, acute kidney injury (AKI) is thought to develop a predisposition toward chronic kidney disease. But the detailed mechanism of the disease progression after AKI is unknown. We made two ischemia-reperfusion injury (IRI) mice models, repaired kidney model and atrophic kidney model, and studied the mechanism that kidney after IRI became atrophy. We found that the atrophy kidney model had two peaks of apoptosis 3 and 14 days after IRI, whereas the repaired kidney model had only one apoptosis peak 3 days after IRI. We showed that the second apoptosis is responsible for the kidney atrophy. Moreover, apoptotic ligands, TNFα and FasL were upregulated at the same time of two apoptosis peaks on the atrophic kidney, and blockade of them before IRI prevented kidney from falling into atrophy. Surprisingly, inhibition of the second apoptosis by anti-TNFα antibody protected from renal atrophy. We propose that apoptosis might play a major role in AKI progression and blockade of TNFα after IRI will be a new therapeutic approach for AKI.

2012-08-10 | GSE39766 | GEO

Microarray-based clustering analysis of miRNAs altered in IRI-AKI mouse kidney

Project description:The aim of this study was to identify miRNAs that regulate AKI and develop their applications as diagnostic biomarkers and therapeutic agents. First, kidney tissues from two different AKI mouse models, namely, AKI induced by the administration of lipopolysaccharide (LPS) causing sepsis (LPS-AKI mice) and AKI induced by renal ischemia–reperfusion injury (IRI-AKI mice), were exhaustively screened for their changes of miRNA expression compared with that of control mice by microarray analysis.

2021-05-14 | GSE172039 | GEO

Microarray-based clustering analysis of miRNAs altered in LPS-AKI mouse kidney

2021-05-14 | GSE172038 | GEO

Evaluation of renal mononuclears cells in acute kidney injury after inhibiting retinoic acid signaling in proximal tubular epithelial cells

Project description:Retinoic acid (RA) signaling is activted in proximal tubular epithelial cells (PTECs) after acute kidney injury (AKI). In these studies we evaluated the functional role of this by inducing ischemia reperfusion-induced AKI (IRI-AKI) in mice after inhibiting RA signaling in PTECs genetically. Here we evaluated the effects of this on the activation of renal mononuclear cells (MNCs) by evaluating RNA expression in CD11B+ cells isolated from kidneys after IRI-AKI. Compared with control mice, there was a reducion in expression of inflammatory marker gene expression 3 days after IRI-AKI in mice with inhibition of RAR signaling in PTECs. These findings suggest a mechanism by which inhibition of RAR signaling in PTECs is protective against AKI.

2023-08-07 | GSE239850 | GEO

The P2Y14/UDP-Glucose pathway is a therapeutic target for ischemic AKI

Project description:Ischemic acute kidney injury (AKI), a complication that frequently occurs in hospital settings, is often associated with hemodynamic compromise, sepsis, cardiac surgery or exposure to nephrotoxicants. AKI is associated with immune cell infiltration into the kidney stroma, which causes acute tubular injury. Here, using a murine renal ischemic-reperfusion injury (IRI) model we show that intercalated cells (ICs) rapidly adopt a pro-inflammatory phenotype post IRI. During the early phase of AKI, we demonstrate that either blocking the pro-inflammatory P2Y14 receptor located on the apical membrane of ICs, or ablation of the gene encoding the P2Y14 receptor in ICs: 1) inhibits IRI-induced chemokine expression increase in ICs; 2) reduces neutrophil and monocyte renal infiltration; 3) reduces the extent of kidney dysfunction; and 4) attenuates proximal tubule (PT) damage. These observations indicate that the P2Y14 receptor participates in the very first inflammatory steps associated with ischemic AKI. In addition, we show that the concentration of the P2Y14 receptor ligand, uridine diphosphate-glucose (UDP-Glc), is higher in urine samples from intensive care unit patients who developed AKI when compared with urine from patients without AKI. In particular, we observed a strong correlation between UDP-Glc concentration and the development of AKI in cardiac surgery patients. Our study identifies the UDP-Glc/P2Y14 receptor axis as a potential target for the prevention and/or attenuation of ischemic-AKI.

2020-03-17 | GSE144522 | 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

Glutamine attenuates renal ischemia-reperfusion injury and prevents acute kidney damage

Project description:Acute kidney injury (AKI) represents a common complication in critically ill patients that is associated with an increased morbidity and mortality. Currently, no effective treatment options are available. Here, we show that glutamine significantly attenuates leukocyte recruitment and inflammatory signaling in human and murine tubular epithelial cells (TECs). In a murine AKI model induced by ischemia-reperfusion-injury (IRI) we show that glutamine causes transcriptomic and proteomic reprogramming in renal TECs and neutrophils, resulting in decreased epithelial apoptosis, neutrophil recruitment and improved mitochondrial functionality and respiration provoked by an ameliorated oxidative phosphorylation. We identify the proteins glutamine gamma glutamyltransferase 2 (Tgm2) and apoptosis signal-regulating kinase (Ask1) as the major targets of glutamine in apoptotic signaling. Increased Tgm2 expression and reduced Ask1 activation result in decreased JNK activation leading to a diminished mitochondrial intrinsic apoptosis in kidneys upon IRI-induced AKI and under hypoxia or following TNFα-treatment of TECs. Consequently, glutamine administration attenuated kidney injury in vivo during AKI progression as well as TEC viability in vitro under inflammatory and hypoxic conditions.

2023-03-11 | PXD029723 | Pride

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