Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell transcriptomics identifies ergothioneine as a mitochondrial protector to prevent AKI-to-CKD progression

ABSTRACT: This study investigates the role and mechanism of ergothioneine (EGT) in mitigating the progression of acute kidney injury (AKI) to chronic kidney disease (CKD). Using a cisplatin-induced mouse model of the AKI-to-CKD transition with EGT intervention, we combined histopathological examination, biochemical assays, and single-cell RNA sequencing (scRNA-seq) to demonstrate that EGT may significantly improve renal function parameters and attenuate renal injury and fibrosis. scRNA-seq analysis revealed that EGT may restore the expression of mitochondrial function-related genes in renal tubular epithelial cells, enhance oxidative phosphorylation and electron transport chain activity, thereby potentially promoting mitochondrial homeostasis. Furthermore, our in vitro experiments confirmed the protective effects of EGT on mitochondria in injured renal tubular epithelial cells, including reducing reactive oxygen species (ROS) generation, restoring diminished mitochondrial membrane potential, and increasing ATP production. These findings elucidate a mechanism by which EGT might delay AKI-to-CKD progression through multi-cellular coordination aimed at improving mitochondrial function, offering a promising therapeutic strategy for kidney diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE329941 | GEO | 2026/07/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Protein lactylation promotes AKI–CKD transition in mice

Project description:Interstitial renal inflammation contributes to the transition from acute kidney injury (AKI) to chronic kidney disease (CKD). Recently, protein lactylation modification has emerged as a novel mechanism mediating chronic organ damage. We investigated lactylated protein profiles and the role of protein lactylation during AKI progression. Severe and moderate AKI mouse models were constructed by bilateral renal ischemia for 35 and 25 min respectively. The lactylation enhancer and inhibitors were used to verify the effect of protein lactylation. Lactylated proteomics was used to detect lactylated protein changes in kidneys, and the lactylated proteins related to kidney injury were screened for verification. We observed significantly higher lactate and protein lactylation levels in the severe than in the moderate AKI model 1–28 days post-injury. Inhibition of protein lactylation protected against renal interstitial fibrosis. In vitro and in vivo experiments demonstrated that protein lactylation activated Nod-like receptor protein 3 (NLRP3) inflammasomes, promoting the AKI–CKD transition. Comprehensive lactylome profiling of severe AKI models revealed a role for lactylated proteins in metabolic pathways, primarily the tricarboxylic acid (TCA) cycle where the rate-limiting enzyme, citrate synthase (CS), exhibited significantly elevated lactylation levels 3–7 days post-AKI induction; K370 was the most significant lysine residue. In vitro, following hypoxia/reoxygenation, the modified/lactylated K370T group significantly decreased CS activity and mitochondrial function. Furthermore, CS-K370 lactylation activated the NLRP3 inflammasome. Lactylation of CS promotes the AKI–CKD transition through NLRP3 inflammasome activation. Inhibition of CS lactylation shows therapeutic potential for preventing this transition.

2025-07-07 | PXD058023 | Pride

Wnt/β-catenin/ATF3 signaling promotes AKI to CKD progression by regulating mitophagy in mice [mouse]

Project description:Sustained activation of Wnt/β-catenin signaling has been shown to promote AKI to CKD progression. However, its underlying mechanisms remain largely unclear. In this study, we investigated this issue via unilateral ischemia/reperfusion injury in mice and hypoxia/reoxygenation (H/R) in HKC-8 cells. Both in vitro and in vivo, overexpression of Wnt1 promoted mitochondrial dynamics and mitophagy damage. Furthermore, we revealed that ATF3 not only is a transcriptional target of canonical Wnt/β-catenin signaling but is also an important pathogenic mediator of kidney disease. ATF3 was expressed in various CKD animal models, including UUO, UIRI, ADR and 5/6NX. In vitro, exogenous ATF3 induced mitochondrial dynamics and mitophagy, and silenced ATF3 expression protected mitochondrial function. Finally, compared with normal individuals, patients with various kidney diseases presented markedly elevated levels of ATF3. In addition, ATF3 levels are closely correlated with renal injury markers and renal fibrosis area in patients. Thus, these results suggest that Wnt/β-catenin/ATF3 signaling activation promotes AKI to CKD progression by regulating mitochondrial dynamics and mitophagy. ATF3 can serve as a promising potential biomarker for AKI to CKD progression.

2026-01-01 | GSE285717 | GEO

Wnt/β-catenin/ATF3 signaling promotes AKI to CKD progression by regulating mitophagy in mice [HKC-8]

2026-01-01 | GSE285716 | GEO

Quinolinic acid metabolism may mitigate AKI to CKD transition

Project description:The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) remains a significant clinical problem with unclear underlying mechanisms. Emerging evidence suggests that alterations in tryptophan metabolism, particularly in the production of downstream metabolites such as quinolinic acid (QA), play a role in renal pathophysiology. QA is a NAD⁺ biosynthesis intermediate metabolized by the enzyme quinolinate phosphoribosyltransferase (QPRT). In this study, we investigated the role of QA in the AKI-to-CKD transition using experimental mouse models and clinical observations and leveraging multiple omics approaches. Systematic metabolomic profiling identified endogenous QA as one of the most significantly elevated metabolites following folic acid-(FA) induced injury. Exogenous QA exacerbated FA-induced kidney dysfunction, demonstrated with several techniques including RNA sequencing. Conversely, aged mice deficient in QPRT showed worsened expression of kidney fibrosis markers even in absence of kidney injury, while younger littermates exhibited worsened induced kidney injury. Mice lacking QA-producing enzymes resisted experimental AKI and AKI-to-CKD progression. Multimodal spatial metabolomics analysis of human AKI kidney biopsies revealed QA accumulation in regions of inflammatory infiltration. Finally, children with CKD exhibited higher urinary QA levels compared to healthy controls. These findings underscore QA as a potential mediator of kidney injury and therapeutic target for preventing the progression from AKI to CKD.

2026-05-23 | GSE332889 | GEO

Targeting WWP2 to restore mitochondrial OXPHOS integrity―a novel strategy to attenuate acute kidney injury to chronic kidney disease transition

Project description:Analysis of kidney from transgenics depleted for renal tubular WW domain containing E3 ubiquitin protein ligase 2 (WWP2) then established a kidney unilateral ischemia reperfusion (UIR) injury in mice induce acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Results provide insight into the role of WWP2 activation in AKI-to-CKD transition.

2026-03-18 | GSE293589 | GEO

Heparin prevents AKI to CKD transition via HDAC1-mediated anti-inflammatory effect independent from its anticoagulant properties

Project description:Aim: This study aimed to investigate the therapeutic potential of heparin, a traditional anticoagulant, in the acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Main methods: Male C57BL/6 mice were subjected to unilateral ischemia-reperfusion (uIR)-induced and folic acid (FA)-induced AKI to CKD mouse model in vivo. Heparin or chemically modified variant devoid of anticoagulant activity (N-Acetyl heparin sodium salt) was administered subcutaneously. Histological analyses, including H&E staining, Masson’s trichrome staining, immunofluorescence, and immunoblotting, were employed to assess renal tubular cell injury, interstitial fibrosis and inflammatory cell infiltration in the kidneys. RNA sequencing of murine kidney cortex tissues was performed to elucidate the mechanistic actions of heparin. Additionally, drug affinity responsive target stability (DARTS) assays and co-immunoprecipitation were conducted to explore the interaction between HDAC1 and heparin. Key findings: We found that low-dose heparin treatment significantly mitigates the AKI to CKD transition, primarily through the suppression of inflammation responses. Mechanistically, heparin binds to HDAC1 in renal tubular epithelial cells, reducing the acetylation of p65，which in turn downregulates the expression of inflammatory factors. Notably, this anti-inflammatory effect of heparin is independent of its anticoagulant activity, as the interaction between heparin and HDAC1 is unrelated to its anticoagulant domain. Furthermore, the chemically modified variant of heparin (N-Acetyl heparin sodium salt), lacking anticoagulant properties, demonstrated a similar protective effect. Significance: Our findings suggest that low-dose heparin, along with its non-anticoagulant derivatives, holds potential as a novel therapeutic approach to attenuate the progression from AKI to CKD.

2026-06-30 | GSE280033 | GEO

VCAM-1 mediates proximal tubule-immune cell cross talk in failed tubule recovery during AKI-to-CKD transition

Project description:Studies in animal models have suggested a linkage between the inflammatory response to injury and subsequent nephron loss during the acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Failure of normal repair during the CKD transition correlates with de novo expression of vascular cell adhesion protein-1 (VCAM-1) by a subset of injured proximal tubule cells. This study identified the role of VCAM-1 expression in promoting the failed repair state. Single-cell transcriptome analysis of patients with AKI and CKD and whole kidney RNA and protein analyses of mouse models of CKD confirmed a marked increase of VCAM-1 expression in the proximal tubules of injured kidneys. In immortalized mouse proximal tubular cells and primary cultured renal cells (PCRCs), VCAM-1 expression was induced by proinflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-1β. Analyses of bulk RNA sequencing of TNF-α-treated primary cultured renal cells or pseudo-bulk RNA sequencing of biopsies from Kidney Precision Medicine Project datasets indicated activation of NF-κB and an enrichment of inflammatory response and cell adhesion pathways in VCAM-1-positive cells. Pharmacological inhibition of NF-κB signaling or genetic deletion of myeloid differentiation factor 88 and TIR domain-containing adapter-inducing interferon-β suppressed TNF-α- and IL-1β-induced VCAM-1 expression in vitro. TNF-α stimulation or overexpression of VCAM-1 significantly increased splenocyte adhesion to the mouse proximal tubular monolayer in culture. These results demonstrate that persistence of proinflammatory cytokines after AKI can induce NF-κB-dependent VCAM-1 expression by proximal tubule cells, mediating increased immune cell adhesion to the tubule and thus promoting further tubule injury and greater risk of progression from AKI to CKD.

2024-09-03 | GSE254359 | GEO

NSD1-916aa encoded by CircNSD1 contributes to AKI-to-CKD transition through inducing ferroptosis in tubular epithelial cells

Project description:Acute kidney injury (AKI) is characterized by a rapid decline in renal function. In severe or recurrent cases, AKI can progress to chronic kidney disease (CKD), marked by renal inflammation and fibrosis. Despite the severity of these outcomes, early-stage diagnostic tools and pharmacological interventions for AKI-to-CKD progression remain limited. In this study, we examined circular RNA (circRNA) expression profiles in mouse renal cortex tissues 14 days post-ischemia/reperfusion (I/R) injury using circRNA sequencing. The renal biopsy samples of patients from AKI patients exhibited reduced CircNSD1 expression, which was inversely associated with inflammation and fibrosis. Overexpression of CircNSD1 attenuated ferroptosis in vivo and in vitro, thereby slowing AKI-to-CKD progression. Mechanistically, CircNSD1 downregulated ACSL4 and SlC39A14 expression through histone H3 lysine 36 (H3K36) methylation, a critical pathway regulating ferroptosis during AKI or hypoxia/reoxygenation (H/R) injury. Furthermore, we identified that CircNSD1 encoded a NSD1-916aa peptide, which may functionally contribute to its observed effect. Collectively, these findings demonstrated that CircNSD1 may serve as a diagnostic and therapeutic target for early detection of AKI-to-CKD transition.

2025-06-22 | GSE299153 | GEO

Ptprz Signaling, Tubule and Macrophage-Mediated Renal Injury and Subsequent Chronic Kidney Disease [TECs]

Project description:Background: Macrophages and tubular epithelial cell interactions are integral in kidney ischemia-incited interstitial inflammation leading to acute kidney injury (AKI). Ischemia/reperfusion injury (I/R) triggers tubular epithelial cells to express IL-34, a macrophage growth factor, that promotes AKI and subsequent CKD. IL-34 engages the cognate receptor, c-FMS, expressed by macrophages, and the recently discovered Protein-Tyrosine Phosphatase Z (Ptprz). Ptprz, binds to multiple ligands other than IL-34 that progressively increase their expression in kidneys after I/R. Methods: We tested the hypothesis that signaling through Ptprz promotes macrophage-mediated AKI and subsequent CKD, by comparing Ptprz knockout (KO) with wild-type (WT) mice after I/R. Results: Ptprz was expressed by leukocytes and in tubular epithelial cells after I/R in mice. Using Ptprz KO mice we determined that during AKI and CKD renal pathology, and loss of renal function were ameliorated. Ptprz-dependent mechanisms mediated: (i) tubular epithelial cell expression of chemokines that fostered macrophage and T cell rich renal inflammation, and (ii) tubule injury and apoptosis, that resulted in the loss of tubules and interstitial fibrosis during CKD. As macrophages release mediators that induce tubular epithelial cell apoptosis, thus Ptprz-dependent mechanisms promote tubule damage. These findings are translational, as after I/R in human kidney transplants, PTPRZ and PTPRZ ligands were upregulated and expressed by the same cell populations as in mice. Moreover, PTPRZ levels in sera were elevated in kidney transplant patients. Conclusion: Intra-renal Ptprz-dependent macrophage and tubular epithelial cell mediated mechanisms promote AKI and subsequent CKD.

2025-07-02 | GSE284134 | GEO

Ptprz Signaling, Tubule and Macrophage-Mediated Renal Injury and Subsequent Chronic Kidney Disease [macrophages]

2025-07-02 | GSE284133 | GEO