Enhancer Regulation in Kidney Repair [RNA-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE114293 | GEO | 2020/05/27
REPOSITORIES: GEO
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Project description:The endogenous repair process of the mammalian kidney allows rapid recovery after acute kidney injury (AKI) through robust proliferation of tubular epithelial cells. There is currently limited understanding of which transcriptional regulators activate these repair programs and how transcriptional deregulation leads to maladaptive repair. Here we investigate the existence of enhancer dynamics in the regenerating mouse kidney.
2020-05-27 | GSE114292 | GEO
Project description:The endogenous repair process of the mammalian kidney allows rapid recovery after acute kidney injury (AKI) through robust proliferation of tubular epithelial cells. There is currently limited understanding of which transcriptional regulators activate these repair programs and how transcriptional deregulation leads to maladaptive repair. Here we investigate the existence of enhancer dynamics in the regenerating mouse kidney.
2020-05-27 | GSE125056 | GEO
Project description:Acute kidney injury (AKI) have been thought to be reversible condition, however, emerging evidence demonstrated association between AKI and subsequent development of irreversible fibrosis and chronic kidney disease. In the present study, since recovery of AKI depends on renal tubular regeneration, factors expressing in renal tubules in adaptive or maladaptive repair process were investigated to predict reversibility of kidney injury. In the kidney of female F344 rats subjected to ischemia/reperfusion (I/R), regenerative tubules and dilated tubules were observed at 3 and 7 days after I/R. In fibrotic areas of the kidney of male SD rats subjected to I/R, renal tubules were dilated or atrophied. From microarray data of regenerative tubules, survivin, sex-determining region Y (SRY)-box 9 (SOX9), and CD44 were extracted as factors possibly relating to tubular regeneration or fibrosis. Immunohistochmical analysis demonstrated that survivin and SOX9 expressed in regenerative tubules, while SOX9 also expressed in renal tubules in fibrotic area, indicating that survivin and SOX9 contribute renal tubular regeneration, but sustained SOX9 expression may lead fibrosis. CD44 expressed in dilated tubules at day 3 and 7, and tubules in fibrotic area, suggesting that CD44 expressed in maladaptive tubules. These information will be helpful to consider reversibility of kidney injury.
2020-06-01 | GSE148420 | 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: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: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
Project description:The kidney has large regenerative capacity that is impeded when injured renal tubular epithelial cells (TECs) undergo SNAI1-driven partial epithelial mesenchymal transition (pEMT). Here we investigate the role of IL11 in TEC pEMT and kidney repair. Wild-type mice with acute kidney injury (AKI) upregulate IL11 in TECs triggering an ERK/P90RSK/GSK3β axis of SNAI1 expression leading to impaired renal function, which is abrogated in Il11 null mice. In mouse models of AKI, a neutralizing IL11 antibody promotes kidney regeneration, while attenuating pEMT, fibrosis and kidney dysfunction. In TECs, TGFβ1 induces autocrine IL11/ERK-dependent pEMT leading to paracrine, IL11-mediated fibroblast activation. Mice with TEC-specific deletion of Il11ra1 are protected from pEMT, inflammation, fibrosis and renal failure. In a mouse model of chronic kidney disease, administration of anti-IL11 reverses fibrosis, regenerates kidney parenchyma and restores renal function. Therapeutic inhibition of IL11 signaling appears permissive for promoting kidney regeneration and improving kidney function.
2022-11-17 | GSE199080 | GEO
Project description:We combined lineage tracing of cycling (Ki67+) cells with single nuclear multiomics (single nucleus RNA-seq + single nucleus ATAC-seq) to characterize the long-term (4 weeks and 6 months) outcome of cells that initiate proliferation early after acute kidney injury (AKI). The data document a broad proliferative response to injury in epithelial and non-epithelial kidney cell types, identify novel transcription factors governing the adaptive and maladaptive proximal tubule cell state and highlight the importance of enhancer dynamics in determining cell states. Comparison of lineage traced with control proximal tubule cells reveals long-term effects of AKI on proximal tubule cells, even following adaptive repair.
2022-11-22 | GSE209610 | GEO
Project description:Acute kidney injury (AKI) is a major health issue, the outcome of which depends primarily on damage and reparative processes of tubular epithelial cells (TEC). Mechanisms underlying AKI remain incompletely understood, specific therapies are lacking and monitoring the course of AKI in clinical routine is confined to measuring urine output and plasma levels of filtration markers. Here we demonstrate feasibility and potential of a novel approach to assess the cellular and molecular dynamics of AKI by establishing a robust urine-to-single cell RNA sequencing (scRNAseq) pipeline for excreted kidney cells via flow cytometry sorting. We analyzed 42,608 single cell transcriptomes of 40 urine samples from 32 AKI patients and compared our data with reference material from human AKI post-mortem biopsies and published mouse data. We demonstrate that TEC transcriptomes mirror intrarenal pathology and reflect distinct injury and repair processes, including oxidative stress, inflammation, and tissue rearrangement. In conclusion, single cell transcriptomics of kidney cells excreted in urine provides non-invasive, unprecedented insight into cellular processes underlying AKI, thereby opening novel opportunities for target identification, AKI sub-categorization and monitoring of natural disease course and interventions.
2022-08-24 | GSE199321 | GEO
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