Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Overexpression of miRNA-5100 with PEI-NPs led to change in expression of many mRNAs

ABSTRACT: 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 followed by quantitative RT-PCR. The initial profiling newly identified miRNA-5100, whose expression levels significantly decreased in kidneys in both LPS-AKI mice and IRI-AKI mice. Next, the administration of miRNA-5100-mimic conjugated with a nonviral vector, polyethylenimine nanoparticles (PEI-NPs), via the tail vein significantly induced miRNA-5100 overexpression in the kidney and prevented the development of IRI-AKI mice by inhibiting apoptosis and inflammation in vivo. Furthermore, serum levels of miRNA-5100 in patients with AKI were identified as significantly lower than those of healthy subjects. ROC analysis showed that the serum expression level of miRNA-5100 can identify AKI (cut-off value 0.14, AUC 0.96, sensitivity 1.00, specificity 0.833, p<0.05). These results suggest that miRNA-5100 regulates AKI and may be useful as a novel diagnostic biomarker and therapeutic target for AKI.

ORGANISM(S): Mus musculus

PROVIDER: GSE172042 | GEO | 2021/05/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

Calycosin inhibited MIF-mediated inflammatory chemotaxis of macrophages to ameliorate ischemia reperfusion-induced acute kidney injury

Project description:Acute kidney disease caused by ischemia-reperfusion (IRI-AKI) is characterized by ectopic inflammation and tubular injury, in which macrophage infiltration and inflammatory activation play a critical pathogenic role. Calycosin is an active flavone from the root of Astragalus membranaceus and shows anti-inflammatory effects in various diseases. In this study, we investigated the renoprotective role of calycosin against IRI-AKI and the underlying mechanism. Our results showed that calycosin treatment reduced the levels of serum creatinine and urea nitrogen along with attenuated tubular necrosis and cast formation in IRI-AKI mice. Calycosin significantly suppressed the activation of NF-κB signaling and the expression of inflammatory mediators IL-1β and TNF-α in IRI-AKI kidneys. In vitro, calycosin inhibited LPS-induced inflammatory activation in RAW 264.7 cells. Interestingly, RNA-seq revealed that calycosin remarkably down-regulated chemotaxis-related pathways in RAW 264.7 cells. Among the differentially expressed genes, Ccl2/MCP-1, a critical chemokine mediating macrophage inflammatory chemotaxis, was down-regulated in both LPS-stimulated RAW 264.7 cells and IRI-AKI kidneys. Consistently, calycosin treatment attenuated macrophage infiltration in the IRI-AKI kidneys. Importantly, in combination with target prediction, molecular docking, and surface plasmon resonance, we showed that calycosin can directly bind to macrophage migration inhibitory factor (MIF). Functionally, calycosin abrogated MIF-stimulated NF-κB signaling activation and Ccl2 expression and MIF-mediated chemotaxis in RAW 264.7 cells without influencing its expression. Collectively, calycosin protects from IRI-AKI by suppressing MIF-mediated macrophage inflammatory chemotaxis. Calycosin could be a promising candidate medicine for clinical treatment of IRI-AKI.

2024-07-28 | GSE247263 | GEO

Proteomic analysis of septic renal acute phase response

Project description:Sepsis-induced acute kidney injury (AKI) is the most common form of AKI with poor outcomes. Renal proteomic analysis after bacterial lipopolysaccharide (LPS) administration revealed that the local renal acute phase reaction (APR) is one of the strongest responses of the kidney during septic AKI in mice. Evaluation of mRNA expression confirmed that most acute phase proteins were produced in the kidney. Our study also provides missing information on the time course of septic renal APR. Proteomic analysis of LPS-induced AKI demonstrated a marked upregulation of local renal acute phase response (APR) that commenced a few hours post injection and peaked at 24 h. Much more APPs were involved in the renal APR than previously identified.

2020-01-08 | PXD014664 | Pride

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

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

tRF-Val-TAC-004 protects against renal ischemia-reperfusion injury via attenuating Apaf1-mediated apoptosis

Project description:tRNA-derived fragments (tRFs) play critical roles in cellular process, and we have previously reported that tRFs is involved in ischemia reperfusion injury induced acute kidney injury (IRI-AKI). However, the precise involvement of tRFs in IRI-AKI remains obscure. This study aims to elucidate the impact of tRF-Val-TAC-004 (tRF-Val) on IRI-AKI and to uncover the underlying mechanisms. Our observations reveal a significant downregulation of tRF-Val in the kidneys of ischemic mice. Overexpression of tRF-Val mitigated renal dysfunction, morphological damage, and tubular cells apoptosis in IRI-AKI mice, while its inhibition exacerbated these effects. Similar outcomes were replicated in CoCl2-treated BUMPT cells upon transfection with tRF-Val mimic or inhibitor. Mechanistically, dual-luciferase reporter assays and AGO-RIP qPCR analyses demonstrated that tRF-Val suppresses Apaf1 expression by targeting the 3’-UTR of Apaf1 mRNA through AGO-dependent sequence complementarity. Furthermore, the protective efficacy of tRF-Val was notably weakened when Apaf1-overexpressing plasmids were transfected into CoCl2-treated BUMPT cells. In summary, these novel findings unveil the protective role of tRF-Val against IRI-AKI through inhibition of Apaf1-mediated apoptosis.

2024-12-18 | GSE282997 | 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

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

Acute cellular injury responses in mouse renal ischemic reperfusion injury

Project description:Acute kidney injury (AKI) is associated with an abrupt loss of kidney function that results in significant morbidity and mortality. Considerable effort has focused around the identification of diagnostic biomarkers and the analysis of molecular events. Most studies have adopted organ-wide approaches that do not fully capture the interplay among different cell types in the pathophysiology of AKI. To extend our understanding of molecular and cellular events in AKI, we developed a mouse line that enables the identification of translational profiles in specific cell types by CRE recombinase-dependent activation of an eGFP-tagged L10a ribosomal protein subunit, and consequently, translating ribosome affinity purification (TRAP) of mRNA populations. By utilizing cell-type specific CRE-driver lines, in this study we identify distinct cellular responses in an ischemia reperfusion injury (IRI) model of AKI. Cell-specific translational expression profiles were uncovered 24 hours after IRI from four populations enriched for distinct anatomical and cellular subgroups: nephron, interstitial cell populations, vascular endothelium, and macrophages/monocytes by Affymetrix microarray.

2014-03-06 | GSE52004 | 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