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DIA-Based Phosphoproteomic Analysis of Kidney Tissues in Mice with Acetaminophen-Induced Kidney Injury

ABSTRACT: Acetaminophen (APAP) overdose can lead to acute kidney injury (AKI), yet its molecular mechanisms remain unclear and no effective treatments are currently available. In this study, we combined transcriptomic, proteomic, and phosphoproteomic profiling of kidneys from APAP-exposed mice to explore molecular mechanisms and potential therapeutic strategies. Ten-week-old male C57BL/6 mice were fasted overnight for 16 hours prior to APAP treatment. Acute kidney injury was induced by intraperitoneal injection of APAP overdose (300 mg/kg body weight) for 6 hours (n = 4). Control mice received an equivalent volume of PBS via intraperitoneal injection (n = 4). Kidney tissues were subsequently collected from APAP-induced kidney injury mice and PBS-injected controls.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Kidney

DISEASE(S): Acute Kidney Tubular Necrosis

SUBMITTER: Jianxin Zheng

LAB HEAD: Jianxin Zheng

PROVIDER: PXD063126 | Pride | 2025-12-05

REPOSITORIES: Pride

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			Action	DRS
	DIA_result.csv	Csv
	README.txt	Txt
	WT_0h_1.raw	Raw
	WT_0h_2.raw	Raw
	WT_0h_3.raw	Raw

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Publications

A multi-omics landscape of programmed cell death in acetaminophen-induced acute kidney injury.

Zheng Jianxin J Lai Peng P Wu Jiaheng J Li Yuqiu Y Chen Fengxian F Zhu Dong D

Renal failure 20251117 1

Acetaminophen (APAP) overdose is a known cause of acute kidney injury, yet the underlying molecular mechanisms remain incompletely understood. In this study, we conducted integrated transcriptomic, proteomic, and phosphoproteomic analyses of kidney tissues from mice with early-stage APAP-induced nephrotoxicity and corresponding controls. A total of 884 genes related to 13 distinct forms of programmed cell death (PCD)-including alkaliptosis, apoptosis, autophagy, cuproptosis, disulfidptosis, ento ...[more]

PMID: 41249093

Similar Datasets

DIA-Based Proteomic Analysis of Kidney Tissues in Mice with Acetaminophen-Induced Kidney Injury

Project description:Acetaminophen (APAP) overdose can cause acute kidney injury (AKI), but its molecular mechanisms remain poorly understood and no effective treatments are currently available. In this study, we performed an integrated analysis combining transcriptomic, proteomic, and phosphoproteomic profiling of kidney tissues from APAP-treated mice to investigate the underlying molecular mechanisms and identify potential therapeutic targets. Ten-week-old male C57BL/6 mice were fasted overnight for 16 hours prior to APAP administration. AKI was induced by intraperitoneal injection of a high dose of APAP (300 mg/kg body weight) for 6 hours (n = 4), while control mice received an equivalent volume of PBS via intraperitoneal injection (n = 4). Kidney tissues were collected from both APAP-treated and control groups for downstream omics analyses.

2025-11-24 | PXD063122 | Pride

A Multi-Omics Landscape of Programmed Cell Death in Acetaminophen-Induced Acute Kidney Injury

Project description:Acetaminophen (APAP) overdose is a known cause of acute kidney injury, yet the underlying molecular mechanisms remain incompletely understood. In this study, we conducted integrated transcriptomic, proteomic, and phosphoproteomic analyses of kidney tissues from mice with early-stage APAP-induced nephrotoxicity and corresponding controls.

2025-12-04 | GSE295115 | GEO

Oplopanax elatus Nakai chlorogenic-enriched fraction protective effect in APAP-induced liver injury

Project description:Purpose: This study investigated the protective effect and further elucidated the mechanisms of action of O. elatus on acetaminophen (APAP)-induced liver injury (AILI). Methods: O. elatus chlorogenic-enriched fraction (OEB) was administrated orally daily for seven consecutive days, followed by a single intraperitoneal injection of an overdose of APAP after the final OEB administration. Results: OEB decreased alanine aminotransferase, aspartate aminotransferase, total cholesterol, total triglycerides contents, regulated superoxide dismutase, catalase, glutathione, malondialdehyde levels, and affected the metabolism of APAP. Furthermore, OEB treatment regulated lipid metabolism, activated the peroxisome proliferator-activated receptors signaling pathway in mice with AILI, affected immune cells, and decreased neutrophil infiltration. Conclusions: This study indicated that OEB is a potential drug candidate for the prevention of APAP-induced hepatotoxicity and elucidated a potential protective mechanism by OEB.

2021-08-20 | GSE182399 | GEO

Single cell RNAseq at 48h and 72h in mice

Project description:Fifty percent of all acute liver failure (ALF) cases in the United States are due to acetaminophen (APAP) overdose. Assessment of canonical features of liver injury, such as plasma alanine aminotransferase activities are poor predictors of acute liver failure (ALF), suggesting the involvement of additional mechanisms independent of hepatocyte death. Previous work demonstrated a severe overdose of APAP results in impaired regeneration, the induction of senescence by p21, and increased mortality. We hypothesized that a discrete population of p21+ hepatocytes acquired a secretory phenotype that directly impedes liver recovery after a severe APAP overdose. Leveraging in-house human APAP explant liver and publicly available singlenuclei RNAseq data, we identified a subpopulation of p21+ hepatocytes enriched in a unique secretome of factors, such as Cxcl14. Spatial transcriptomics in the mouse model of APAP overdose confirmed the presence of a p21+ hepatocyte population that directly surrounded the necrotic areas. In both male and female mice, we found a dose-dependent induction of p21 and persistent circulating levels of the p21-specific constituent, Cxcl14, in the plasma after a severe APAP overdose. In parallel experiments, we targeted either the putative senescent hepatocytes with the senolytic drugs, dasatinib and quercetin, or Cxcl14 with a neutralizing antibody. We found that targeting Cxcl14 greatly enhanced liver recovery after APAP-induced liver injury, while targeting the senescent hepatocyte had no effect. This data supports that the sustained induction of p21 in hepatocytes with persistent Cxcl14 secretion are critical mechanistic events leading to ALF in mice and human patients.

2024-04-15 | GSE255834 | GEO

RNAseq on Human APAP-ALF

2024-04-15 | GSE255777 | GEO

Adipose-derived mesenchymal stem cells inhibit JNK-mediated mitochondrial retrograde pathway to alleviate acetaminophen-induced acute liver injury

Project description:Acetaminophen (APAP) is the major cause of drug-induced liver injury, with limited treatment options. APAP overdose invokes excessive oxidative stress that triggers mitochondria-to-nucleus retrograde pathways, contributing to APAP-induced liver injury (AILI). Mesenchymal stem cell therapy is a promising tool for acute liver failure. Therefore, the purpose of this study is to investigate the beneficial effects of adipose-derived mesenchymal stem cell (AMSC) therapy on AILI and reveal the potential therapeutic mechanisms. C57BL/6 mice are used as the animal model and AML12 normal murine hepatocytes as the cellular model of APAP overdose. Immunohistochemical staining, western blotting, immunofluorescence staining, and RNA sequencing assay are used for assessing the efficacy and validating mechanisms of AMSC therapy. We found AMSC therapy effectively ameliorated AILI, while delayed AMSC injection lost its efficacy related to the c-Jun N-terminal kinase (JNK)-mediated mitochondrial retrograde pathways. We further found that AMSC therapy inhibited JNK activation and mitochondrial translocation, reducing APAP-induced mitochondrial damage. The down-regulation of activated Ataxia telangiectasia mutated (ATM) and DNA damage response proteins in AMSC treated mice liver indicated AMSC blocked the JNK-ATM pathway. Overall, AMSC may be an effective treatment for AILI by inhibiting JNK-ATM mitochondrial retrograde pathway, which improves APAP-induced mitochondrial dysfunction and liver injury.

2022-12-17 | GSE218879 | GEO

E3 ubiquitin ligase NEDD4-1 suppresses acetaminophen-induced liver injury in mouse by targeting the degradation of VDAC1

Project description:Acetaminophen (APAP) overdose provokes various degrees of liver injury, whose pathogenesis involves multiple pathological events, such as mitochondrial damage and necrosis. E3 ubiquitin ligase neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) plays vital roles in regulating a wide spectrum of physiological processes, and has been implicated in the pathogenesis of numerous liver disease. However, studies about the regulation of NEDD4-1 on APAP-induced liver injury (AILI) is still deficient. Thus, the aim of this study is to determine whether and how NEDD4-1 plays a role in AILI. Thus, we performed transcriptomic studies comparing liver samples of APAP-treated Flox or APAP-treated hepatocyte-specific Nedd4-1 (HepKO) deficiency mice,

2022-03-29 | GSE199353 | GEO

Role of YAP in Liver Regeneration After Acetaminophen Overdose

Project description:Overdose of acetaminophen (APAP) is the major cause of acute liver failure in the Western world with very limited treatment options. Previous studies from our groups and others have shown that timely activation of liver regeneration is a critical determinant of transplant-free survival of APAP-induced acute liver failure (ALF) patients. We used affy microarrays to explore the mechanisms of transcriptional expression in YAP-KO mice after 300mg/kg APAP overdose.

2021-10-04 | GSE183119 | GEO

Transcription profiling of mouse liver after Acetaminophen intoxication

Project description:Acetaminophen (APAP) is the most widely used analgesic in the United States. Its acute overdose causes liver damage by inducing localized centrilobular cell death. Because of widespread use, APAP toxicity has become the most frequent cause of acute liver failure. Many factors have been associated with the susceptibility of APAP-induced liver injuries, however, few of them have been confirmed and used in the clinical setting. We tried to identify the subset of factors that could affect susceptibility to APAP-induced liver injury by an integrative genetic, transcriptional and 2-D-NMR-based metabolomic analysis across a panel of inbred mouse strains. Experiment Overall Design: After a single administration of high dose (300 mg/kg i.p.) APAP, liver and blood samples were extracted from 3 sensitive (C57B6, DBA/2, and SmJ) and 1 resistant (SJL) mice strains at 0, 3 and 6 hour after APAP exposure. Endogenous metabolites from liver samples were analyzed by 1H-13C 2-dimensional-NMR and gene expression changes occurring within these liver samples were simultaneously analyzed using Affymetrix microarrays. The transcriptional and metabolomic data was jointly analyzed, and functional information within the Gene Ontology database was used to identify the subset of genes that could affect susceptibility to APAP-induced liver injury in the early phase response.

2009-08-23 | E-GEOD-17649 | biostudies-arrayexpress

Expression data from mouse liver after Acetaminophen intoxication

2009-08-14 | GSE17649 | GEO