Differential RNA expression in kidney of mice with septic AKI induced by lipopolysaccharide
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE227623 | GEO | 2023/04/03
REPOSITORIES: GEO
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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
Project description:Sepsis-associated acute kidney injury (SA-AKI) is a severe and life-threatening condi-tion with high morbidity and mortality among emergency patients, and it poses a sig-nificant risk of chronic renal failure. Clinical treatments for SA-AKI remain reactive and non-specific, lacking effective diagnostic biomarkers or treatment targets. In this study, we established an SA-AKI mouse model using LPS and performed proteomics and metabolomics analyses. A variety of bioinformatic analyses, including Gene Set En-richment Analysis (GSEA), Weighted Gene Co-expression Network Analysis (WGCNA), protein and protein interactions (PPI), and MetaboAnalyst analysis, were conducted to investigate the key molecules of SA-AKI. Proteomics and metabolomics analyses re-vealed that sepsis led to impaired renal mitochondrial function and metabolic disorders. Immune-related pathways were found to be activated in kidneys upon septic infection. The catabolic products of polyamines accumulated in septic kidneys. Overall, our study provides a more comprehensive understanding of SA-AKI and identifies potential pathways for this condition.
2023-10-24 | PXD044371 | Pride
Project description:Mouse urine proteome in case of septic AKI
2013-07-08 | PRD000453 | Pride
Project description:Renal hypoxia is widespread in acute kidney injury (AKI) of various aetiologies. Hypoxia adaptation, conferred through the hypoxia-inducible factor (HIF), appears to be insufficient. Here we show that HIF activation in renal tubules through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO) protects from rhabdomyolysis-induced AKI. In this model, histological observations indicate that injury mainly affects proximal convoluted tubules, with 5% necrosis at d1 and 40% necrosis at d2. HIF-1alpha up-regulation in distal tubules reflects renal hypoxia. However, lack of HIF in proximal tubules suggests insufficient adaptation by HIF. AKI in VHL-KO mice leads to prominent HIF activation in all nephron segments, as well as to reduced serum creatinine, serum urea, tubular necrosis, and apoptosis marker caspase-3 protein. At d1 after rhabdomyolysis, when tubular injury is potentially reversible, HIF mediated protection in AKI is associated with activated glycolysis, cellular glucose uptake and utilization, autophagy, vasodilation, and proton removal as demonstrated by qPCR, pathway enrichment analysis and immunohistochemistry. Together, our data provide evidence for a HIF-orchestrated multi-level shift towards glycolysis as a major mechanism for protection against acute tubular injury. All experiments were carried out in transgenic mice in which selective renal tubular VHL knockout (VHL-KO) was inducible by doxycycline (Reference: Mathia S, Paliege A, Koesters R, Peters H, Neumayer HH, Bachmann S, Rosenberger C. Action of hypoxia-inducible factor in liver and kidney from mice with Pax8-rtTA-based deletion of von Hippel-Lindau protein. Acta Physiol (Oxf). 2013; 207(3):565-76.). Four groups of animals were used: 1) controls: untreated mice; 2) VHL-KO: injected with doxycycline (0.1 mg per 10 g body weight SC), 4 days prior to sacrifice; 3) AKI: rhabdomyolysis; 4) VHL-KO/AKI: doxycycline plus rhabdomyolysis. To induce AKI, 50% glycerol (0.05 ml per 10 g body weight) was injected IM into the left hind limb under isoflurane narcosis. Drinking water was withdrawn between 20 h prior and 24 h after glycerol injection.
2013-09-05 | E-GEOD-44925 | biostudies-arrayexpress
Project description:Sepsis induced acute kidney injury (AKI) is associated with a rapid decline of kidney function, leading to unacceptably high morbidity and mortality rate as well as progression to chronic kidney disease (CKD). We have recently developed a septic AKI mouse model. By quantitatively assessing the kidney proteome and phosphoproteome changes upon bacterial infection, we accurately quantified over 2,200 kidney proteins with high confidence, which provided us the first global overview of the extensively remodeled kidney proteome and revealed widespread metabolic and oxidation-reduction processes undergone in septic kidney. This data will give us unprecedented insight into how renal cells response to microbe invasion, and will likely serve as a reference dataset of systems biology.
2020-09-25 | PXD017045 | Pride
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
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 | GSE172038 | GEO
Project description:CD4+ T cells mediate the pathogenesis of ischemic and nephrotoxic acute kidney injury (AKI), as well as acute injury to other organs. However, the underlying mechanisms of CD4+ T cell-mediated pathogenesis are largely unknown. We therefore conducted unbiased RNA-sequencing to discover novel mechanistic pathways of kidney CD4+ T cells post-ischemia compared to normal mouse kidney. Unexpectedly, lipocalin-2 (Lcn2) gene, which encodes neutrophil gelatinase-associated lipocalin (NGAL) had the highest (~60)-fold increase. The NGAL increase in CD4+ T cells during AKI was confirmed at the mRNA level with real-time PCR and at the protein level with ELISA. NGAL is a potential biomarker for the early detection of AKI and has multiple potential biological functions during organ injury. However, the role of NGAL produced by CD4+ T cells has not been investigated. We found that ischemic AKI in NGAL knockout (KO) mice had worse renal outcomes compared to wild type (WT) mice. Adoptive transfer of NGAL-deficient CD4+ T cells from NGAL KO mice into CD4 KO or WT mice led to worse renal function than transfer of WT CD4+ T cells. In vitro simulated ischemia reperfusion showed that NGAL-deficient CD4+ T cells express higher levels of IFN-γ mRNA compared to WT CD4+ T cells. In vitro differentiation of naive CD4+ T cells to Th17, Th1 and Th2 cells led to significant increase in Lcn2 expression. Human kidney CD4+ T cell NGAL also increased significantly post-ischemia. These results demonstrate an important role for CD4+ T cell NGAL as a mechanism by which CD4+ T cells mediate AKI and extend the importance of NGAL in AKI beyond diagnostics.
2019-11-25 | GSE139171 | GEO
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
Project description:PTBA has been published to increase renal tubular cell proliferation, increased survival, and increased renal functional recovery in fish and various models of murine models of acute kidney injury. Immunohistological analyses suggested increased cell proliferation is accompanied by increased epithelial-to-mesenchymal transition in the RTECs. In order to elucidate pathways responsible for the increased repair response after compound treatment, larval zebrafish were given AKI and treated with PTBA analogue, UPHD25 or DMSO. Results suggests that epithelial-related genes were downregulated while mesenchymal-related genes were upregulated with injury and compound treatment. Results further validate our immunohistological finding that our compound increase post-AKI repair by increasing EMT in renal tubular cells.
2019-03-25 | GSE126418 | GEO