Similar Datasets
Project description:Acute kidney injury (AKI) represents a syndrome seldom characterized by a single, distinct pathophysiological cause. Rhabdomyolysis-induced acute kidney injury (RIAKI) constitutes roughly 15% of AKI cases, yet its underlying pathophysiology remains poorly understood. Using a murine model of RIAKI induced by muscular glycerol injection, we aimed to analyse transcriptomic alterations by RNAseq.
2024-09-18 | GSE264651 | GEO
Project description:In acute kidney injury (AKI) regions of the kidney are hypoxic. However, for reasons yet unknown, adaptation to hypoxia through hypoxia inducible factor (HIF) is limited. Here we seek for potential HIF repressors, their amenability to intervention, and assess the consequences for AKI outcome Renal miR-22 is up-regulated in AKI. In vitro, miR-22 is inducible by hypoxia, represses HIF, and this repression is offset by specific anti-miR-22 molecules. Inhibition of miR-22 in AKI leads to a complex regulation of more than 3,000 renal genes, most of which are unrelated to the HIF pathway.
2019-11-20 | GSE107710 | GEO
Project description:Rhabdomyolysis is a severe condition caused by skeletal muscle damage, leading to acute kidney injury (AKI). We demonstrate that complement has a direct pathogenic role in rhabdomyolysis-induced AKI. Deposition of C3d in the tubules of patients and mice correlated with rhabdomyolysis-induced AKI. Moreover, C3-defiient mice with rhabdomyolysis had preserved renal function. Mechanistically, C3-deficiency attenuated strongly inflammatory and apoptotic components of the renal transcriptome, perturbed by rhabdomyolysis. Complement was activated intrarenal by the lectin pathway via collectin-11. It proceeded in a C4-bypass manner and was amplified by heme-activated alternative pathway. Therefore, complement and heme are promising therapeutic targets for rhabdomyolysis-induced AKI.
2020-11-01 | GSE153507 | GEO
Project description:Microarray analysis of human kidneys with acute kidney injury (AKI) has been limited because such kidneys are seldom biopsied. However, all kidney transplants experience AKI, and early kidney transplants without rejection are an excellent model for human AKI: they are screened to exclude chronic kidney disease, frequently biopsied, and have extensive follow-up. We used histopathology and microarrays to compare indication biopsies from 28 transplants with AKI to 11 pristine protocol biopsies of stable transplants. Kidneys with AKI showed increased expression of 394 injury-repair response associated transcripts, including many known epithelial injury molecules (e.g. ITGB6, LCN2), tissue remodeling molecules (e.g. VCAN), and inflammation molecules (S100A8, ITGB3). Many other genes also predict the phenotype, depending on statistical filtering rules, including AKI biomarkers as HAVCR1 and IL18. Most mouse orthologs of the top injury-repair transcripts were increased in published mouse AKI models. Pathway analysis of the injury-repair transcripts revealed similarities to cancer, development, and cell movement. The injury-repair transcript score AKI kidneys correlated with reduced function, future recovery, brain death, and need for dialysis, but not future graft loss. In contrast, histologic features of "acute tubular injury" did not correlate with function or with the molecular changes. Thus the injury-repair associated transcripts represent a massive coordinate injury-repair response of kidney parenchyma to AKI, similar to mouse AKI models, and provide an objective measure for assessing the severity of AKI in kidney biopsies and validation for the use of many AKI biomarkers. AKI biopsies sample names and CEL files are from GSE21374. All consenting renal transplant patients undergoing biopsies for cause as standard of care between 09/2004 and 10/2007 at the university of Alberta or between 11/2006 and 02/2007 at the University of Illinois were included in the analysis. In addition to the cores required for standard histopathology, we collected one core for gene expression studies. the relationship between gene expression in the biopsy and subsequent graft loss was analyzed. This dataset is part of the TransQST collection.
2012-02-21 | E-GEOD-30718 | biostudies-arrayexpress
Project description:Background: Rhabdomyolysis (RM) is a clinical syndrome characterized by breakdown of skeletal muscle fibers and release of their contents into the circulation. Myoglobin-induced acute kidney injury (AKI) is one of the most severe complications of RM. Based on our previous research, exogenous biological renal support alleviates renal ischemia-reperfusion injury in elderly mice. This study aimed to determine whether exogenous biological renal support promotes renal recovery from RM-induced AKI and to preliminarily explore the mechanisms involved. Methods: A parabiosis animal model was established to investigate the effects of exogenous biological renal support on RM-induced AKI. Mice were divided into three groups: the control group (in which mice were injected with sterile saline), the RM group (in which mice were injected with 8 mL/kg glycerol), and the parabiosis + RM group (in which recipient mice were injected with glycerol 3 weeks after parabiosis model establishment). Blood samples and kidney tissue were collected for further processing 48 h after RM induction. Bioinformatics analysis was conducted via Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, functional enrichment analysis, and clustering analysis. Results: No mice died within 48 h after the procedure. Exogenous biological renal support attenuated the histological and functional deterioration in mice with RM-induced AKI. Bioinformatics analysis identified key pathways and proteins involved in this process. We further demonstrated that exogenous biological renal support ameliorated AKI through multiple mechanisms, including by suppressing the complement system; attenuating oxidative stress, inflammation, and cell death; and increasing proliferation. Conclusions: Exogenous biological renal support provided by parabiosis can improve renal function in RM-induced AKI by suppressing the complement system; decreasing oxidative stress, inflammation, and cell death; and promoting tubular cell proliferation. Our study provides basic research evidence for the use of bioartificial kidneys to treat RM-induced AKI.
| S-EPMC8193099 | biostudies-literature
Project description:Acute kidney injury (AKI) is a commonly observed but poorly understood clinical syndrome. Keratin 20 (KRT20), a key component of intermediate filaments, is generally known as a biomarker of renal tubular injury, but its role in kidney disease remains unclear. By bioinformatics analysis and further laboratory validation, we confirmed that expression of KRT20 was highly upregulated in the renal proximal tubular cells (RPTC) during the early phase of AKI prior to the rise of KIM1 gene expression. We reported here that KRT20 was upregulated via Fosb in the kidneys of ischemia/reperfusion injury and cisplatin-nephrotoxic AKI mice. Knockout of KRT20 specifically in RPTC aggravated AKI. Mechanistically, KRT20 protected against AKI by sequestering peroxiredoxin 2 (PRDX2), an antioxidant protein, to prevent renal tubular cell ferroptosis. Specifically, KRT20 bound to PRDX2 to suppress its exosomal secretion from kidney tubular cells. We further found that ALG-2-interacting protein X (Alix) interacts with PRDX2 to mediate its exosomal secretion and KRT20 competed with Alix to interact with PRDX2 at its N terminal domain and thereby inhibiting its exosomal secretion. Finally, we showed that the expression of KRT20 and PRDX2 correlated with kidney injury and decline of renal function in AKI patients. In conclusion, KRT20 is upregulated in early AKI to protect kidney tubule cells by sequestering PRDX2 and inhibiting ferroptosis. KRT20 could be an early biomarker for AKI and a potential drug target for AKI prevention and therapy.
2025-06-30 | GSE278358 | GEO
Project description:Microarray analysis of human kidneys with acute kidney injury (AKI) has been limited because such kidneys are seldom biopsied. However, all kidney transplants experience AKI, and early kidney transplants without rejection are an excellent model for human AKI: they are screened to exclude chronic kidney disease, frequently biopsied, and have extensive follow-up. We used histopathology and microarrays to compare indication biopsies from 28 transplants with AKI to 11 pristine protocol biopsies of stable transplants. Kidneys with AKI showed increased expression of 394 injury-repair response associated transcripts, including many known epithelial injury molecules (e.g. ITGB6, LCN2), tissue remodeling molecules (e.g. VCAN), and inflammation molecules (S100A8, ITGB3). Many other genes also predict the phenotype, depending on statistical filtering rules, including AKI biomarkers as HAVCR1 and IL18. Most mouse orthologs of the top injury-repair transcripts were increased in published mouse AKI models. Pathway analysis of the injury-repair transcripts revealed similarities to cancer, development, and cell movement. The injury-repair transcript score AKI kidneys correlated with reduced function, future recovery, brain death, and need for dialysis, but not future graft loss. In contrast, histologic features of "acute tubular injury" did not correlate with function or with the molecular changes. Thus the injury-repair associated transcripts represent a massive coordinate injury-repair response of kidney parenchyma to AKI, similar to mouse AKI models, and provide an objective measure for assessing the severity of AKI in kidney biopsies and validation for the use of many AKI biomarkers.
2012-02-21 | GSE30718 | GEO
Project description:Acute kidney injury (AKI) is a common cause of chronic kidney disease, but the pathogenic mechanisms remain unclear and treatments remain limited. Here we report that Annexin A13 (ANXA13), the founder member of Annexins is renal protective in AKI. Clinically, ANXA13 was lost in the AKI kidney in both patients and ischemic-reperfusion injury (IRI)-induced mice. This was associated with declined serum levels of ANXA13 but elevated urinary ANXA13. To explore the functional role of ANXA13 in AKI, we kidney-specifically overexpressed ANXA13 and found that overexpressing ANXA13 protected against IRI-AKI by significantly inhibiting tubular necrosis and lowering serum creatinine. In contrast, kidney-specifically silencing ANXA13 largely promoted AKI. Mechanistically, renal ANXA13 was downregulated by TGF-β1 via Smad3 signaling as mice lacking Smad3 were protected from the loss of renal ANXA13 and the development of AKI. More importantly, we also uncovered that ANXA13 could directly bind TGF-β receptor type 1 and inhibit its phosphorylation, thereby inactivating Smad3 signaling and Smad3-mediated tubular cell death via the p21-dependent G1cell cycle arrest. In conclusion, ANXA13 is renal protective and may be a potential new biomarker and a novel therapeutic agent for AKI.
2026-02-25 | GSE269541 | GEO
Project description:Contrast-induced acute kidney injury (CI-AKI) is typically defined by an increase in serum creatinine (SCr) after intravascular administration of contrast medium. Since creatinine is an unreliable indicator for acute changes in kidney function, an early biomarkers for CI-AKI diagnosis is important for initiating therapy.We assessed the hypothesis that circulating microRNAs (miRNAs) could be served as potential biomarkers to early detect CI-AKI.The rat model of acute kidney injury was developed as we previously described. We first detect miRNA profile of plasma and kidney tissue using Agilent microarray platform. 3 miRNA species with > 1.5-fold increase in plasma samples of CI-AKI rats, including miRNA-30a, miRNA-30e and miRNA-188, were selected as candidate miRNAs of potential biomarkers. 24 rats were randomly divided into 2 groups (CI-AKI group and control group), each with 4 subgroups (n=3). Peripheral blood and kidney samples were harvest at 8h after contrast medium/normal saline administration. Total RNA sample from each rat in the same subgroup was combined together as pooled sample for further test. The Agilent microarray platform was adapted to profile the miRNA spectra.
2016-05-14 | E-GEOD-81400 | biostudies-arrayexpress
Project description:Rhabdomyolysis is a risk factor for acute kidney injury, transition towards chronic kidney disease, and death. The role of calcium phosphate deposits in the mechanisms of rhabdomyolysis-induced acute kidney injury (RAKI) is still unclear. Better insight of the role calcium in RAKI could lead to new therapeutic avenues. Here, we show in a mice model of RAKI that calcium phosphate deposits were frequent in the kidney (hydroxyapatite) and partly correlated with the severity of the kidney injury. However, the intensity of deposits was highly heterogeneous between mice. Treatment with sodium chloride, sodium bicarbonate or inorganic pyrophosphate (PPi; an inhibitor of the calcium phosphate crystallization), or combinations thereof, did not improve kidney outcomes and hydroxyapatite deposition during RAKI. Unexpectedly, Abcc6 knockout mice (ko), characterized by PPi deficiency, developed less severe RAKI despite similar rhabdomyolysis severity, and had similar hydroxyapatite deposition suggesting alternative mechanisms. This improved kidney outcome at day 2 translated to a trend in improved glomerular filtration rate at month 2 in Abcc6-/-mice and to significantly less interstitial fibrosis. In addition, whereas the pattern of infiltrating cells at day 2 was similar between wt and ko mice, kidneys of Abcc6-/- mice were characterized by more CD19+ B-cells, less CD3+ T-cells and a lower R1/R2 macrophage ratio at month 2. In summary, kidney calcium phosphate deposits are frequent in RAKI but hydration with sodium bicarbonate or sodium chloride does not modify the kidney outcome. Blocking ABCC6 emerges as a new option to prevent RAKI and subsequent transition toward kidney fibrosis.
| S-EPMC10700332 | biostudies-literature