Renal congestion exacerbates acute kidney injury in mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA702099 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13720976.fastq.gz | Fastqsanger.gz | |||
| SRR13720977.fastq.gz | Fastqsanger.gz | |||
| SRR13720978.fastq.gz | Fastqsanger.gz | |||
| SRR13720979.fastq.gz | Fastqsanger.gz | |||
| SRR13720980.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:The number of heart failure (HF) patients is increasing. HF is frequently accompanied by kidney dysfunction and such organ failure is closely related. Recent investigations revealed that increased renal venous pressure, rather than decreased cardiac output, causes the deterioration of kidney function in HF patients; however, the underlying responsible mechanisms are unknown. We demonstrated that reduced blood flow speed in peritubular capillaries (PTCs) by renal congestion and upregulation of nuclear factor-κB (NF-κB) signaling synergistically exacerbate kidney injury. We generated a novel mouse model with unilateral renal congestion by coarctation of the inferior vena cava between renal veins. Intravital imaging highlighted the notable dilatation of PTCs and decreased renal blood flow speed in the congestive kidney. Renal damage after ischemia reperfusion injury was exacerbated in the congestive kidney and accumulation of polymorphonuclear leukocytes (PMNs) within PTCs was observed at the acute phase after injury. Pharmacological inhibition of NF-κB ameliorated renal congestion-mediated exacerbation of kidney injury. In vitro, adhesion of PMNs on the TNFα-stimulated endothelial cells was accelerated by perfusion of PMNs at a slower speed, which was cancelled by the inhibition of NF-κB signaling. Our study demonstrates the importance of slower blood flow accompanying activated NF-κB signaling in the congestive kidney in the exacerbation of renal injury. These mechanisms may explain how increased renal venous pressure in HF patients causes the deterioration of kidney dysfunction. Inhibition of NF-κB signaling may be a therapeutic candidate for the vicious cycle between heart and kidney failure with increased renal venous pressure.
2024-02-16 | GSE166838 | GEO
Project description:Epidemiological studies showed that patients with heart failure frequently develop kidney dysfunction, called cardio-renal syndrome (CRS). Elevated central venous pressure rather than low cardiac output strongly correlates with worsening renal function, and is being increasingly recognized as the pathophysiology responsible for CRS. However, due to the lack of appropriate animal models, the molecular mechanisms underlying the congestion-mediated acceleration of kidney injury, called renal congestion, remain unclear. In the present study, using a novel mouse renal congestion model, we detected injured tubule-specific cell-cell interactions in congestive kidneys and showed that Cellular Communication Network Factor 1 (CCN1) played an important role in this process. Transcriptomics of kidneys with ischemia-reperfusion injury (IRI) and renal congestion revealed the up-regulation of paracrine chemokine-related pathways. The up-regulation of CCN1 was observed in the acute phase after kidney injury with renal congestion. Positive staining for phosphorylated focal adhesion kinase (pFAK), a downstream signaling molecule of CCN1, was noted in fibroblasts at injury sites in congestion-IRI kidneys. CCN1 activated the phosphorylation of FAK and ERK in vitro, which accelerated the migration of fibroblasts and macrophages. We then examined the effects of CCN1 deletion in tubular epithelia on congestion-mediated kidney injury in vivo. pFAK expression in injury sites was down-regulated in CCN1-KO mice, and the congestion-mediated worsening of tissue fibrosis was significantly ameliorated. In conclusion, we herein demonstrated the important role of injured tubule-derived CCN1 on pFAK-mediated fibroblast migration in congestive kidneys. The inhibition of CCN1 has potential as a therapeutic candidate for preventing the transition of renal congestion-mediated kidney injury to fibrosis.
2025-07-09 | GSE283859 | GEO
Project description:Injured tubule-derived CCN1 exacerbates renal congestion-mediated acute kidney injury and fibrosis
| PRJNA1195921 | ENA
Project description:We created a rat renal congestion model and investigated the effect of renal congestion on hemodynamics and molecular mechanisms. The inferior vena cava (IVC) between the renal veins was ligated by suture in male Sprague-Dawley rats to increase upstream IVC pressure and induce congestion in the left kidney only. Left kidney congestion reduced renal blood flow, glomerular filtration rate, and increased renal interstitial hydrostatic pressure. Tubulointerstitial and glomerular injury and medullary thick ascending limb hypoxia were observed only in the congestive kidneys. Molecules related to extracellular matrix expansion, tubular injury, and focal adhesion were upregulated in microarray analysis. Renal decapsulation ameliorated the tubulointerstitial injury. Electron microscopy captured pericyte detachment in the congestive kidneys. Transgelin and platelet-derived growth factor receptors, as indicators of pericyte-myofibroblast transition, were upregulated in the pericytes and the adjacent interstitium. With the compression of the peritubular capillaries and tubules, hypoxia and physical stress induce pericyte detachment, which could result in extracellular matrix expansion and tubular injury in renal congestion.
2018-11-14 | GSE114031 | GEO
Project description:Renal congestion exacerbates acute kidney injury in mice
| PRJDB11205 | ENA
Project description:Our study investigates how the systemic administration of glutamine modulates the transcriptomic profile of neutrophils and renal tubular epithelial cells in the kidney during acute kidney injury.
2021-11-13 | GSE188628 | GEO
Project description:Acute Kidney Injury (AKI) is a rapid renal function decline associated with pronounced morbidity and mortality. Single Cell RNA Sequencing is a powerful tool allowing for examining transcriptional changes in multiple renal cell populations involved in the injury response. Our study reveals renal developmental gene re-activation and lineage infidelity in response to ischemia/reperfusion induced AKI, along with the novel genes which might serve as markers of acute kidney disease
2020-10-30 | GSE139506 | GEO
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
Project description:Inflammation plays an essential role in eliminating microbial pathogens and repairing tissues, while sustained inflammation accelerates kidney damage and disease progression. Therefore, understanding the mechanisms of the inflammatory response is vital for developing therapies for inflammatory kidney diseases like acute kidney injury (AKI), which currently lacks effective treatment. Here, we identified N-acetyltransferase 10 (NAT10) as a significant mediator of inflammation. NAT10, the only known ‘writer’ protein for N4-acetylcytidine (ac4C) acetylation, is elevated in renal tubules across various AKI models, human biopsies and cultured tubular epithelial cells (TECs). Conditional knockout (cKO) of NAT10 in mouse kidneys attenuates renal dysfunction, inflammation, and infiltration of macrophages and neutrophils, whereas its conditional knock-in (cKI) exacerbates these effects. Mechanistically, our findings from ac4C-RIP-seq and RNA-seq analyses reveal that NAT10-mediated ac4C acetylation enhances the mRNA stability of a range of key chemokines, including C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 1(CXCL1), promoting macrophage and neutrophil recruitment and accelerating renal inflammation. Additionally, CCL2 and CXCL1 neutralizing antibodies or their receptor inhibitors, abrogated renal inflammation in NAT10-overexpression TECs or NAT10-cKI mice. Importantly, inhibiting NAT10, either through Adeno-associated virus 9 (AAV9)-mediated silencing or pharmacologically with our newly identified inhibitor Cpd-155, significantly reduces renal inflammation and injury. Thus, targeting the NAT10/CCL2/CXCL1 axis presents a promising therapeutic strategy for treating inflammatory kidney diseases.
2025-04-10 | GSE286352 | GEO
Project description:Background: The inflammatory response to acute kidney injury (AKI) likely dictates future renal health. Lymphatic vessels are responsible for maintaining tissue homeostasis through transport and immunomodulatory roles. Due to the relative sparsity of lymphatic endothelial cells (LECs) in the kidney, past sequencing efforts have not characterized these cells and their response to AKI. Methods: Here we characterized murine renal LEC subpopulations by single-cell RNA sequencing and investigated their changes in cisplatin AKI 72 hours post injury. Data was processed using the Seurat package. We validated our findings by qPCR in LECs isolated from both cisplatin-injured and ischemia reperfusion injury, by immunofluorescence, and confirmation in in vitro human LECs. Results: We have identified renal LECs and their lymphatic vascular roles that have yet to be characterized in previous studies. We report unique gene changes mapped across control and cisplatin injured conditions. Following AKI, renal LECs alter genes involved in endothelial cell apoptosis and vasculogenic processes as well as immunoregulatory signaling and metabolism. Differences between injury models were also identified with renal LECs further demonstrating changed gene expression between cisplatin and ischemia reperfusion injury models, indicating the renal LEC response is both specific to where they lie in the lymphatic vasculature and the renal injury type. Conclusions: In this study, we uncover lymphatic vessel structural features of captured populations and injury-induced genetic changes. We further determine LEC gene expression is altered between injury models. How LECs respond to AKI may therefore be key in regulating future kidney disease progression.
2024-02-20 | GSE236199 | GEO