PXD063359-1

PXD063359 is an original dataset announced via ProteomeXchange.

Title	Integrated multi-omics analysis of liver metabolic dysregulation in ACE2 knockout mice
Description	This study systematically investigated the impact of ACE2 knockout (ACE2KO) on hepatic metabolic homeostasis and its molecular mechanisms, using integrated transcriptomic, proteomic, and metabolomic profiling. ACE2 deficiency exacerbates hepatic lipid accumulation, as evidenced by elevated total cholesterol and triglyceride levels, while disrupting the renin-angiotensin system equilibrium via increased angiotensin II (Ang II) and reduced Ang-(1-7). Histopathological analysis revealed hepatocyte edema, vacuolar degeneration, and inflammatory infiltration in the ACE2KO mice. Multi-omics integration uncovered systemic metabolic dysregulation: transcriptomics identified 1,004 differentially expressed genes (DEGs), including lipid metabolism regulators (Scd1, Fabp1) and circadian rhythm modulators (Arntl, Cry1), 191 differentially expressed proteins (DEPs) associated with interferon signaling activation (Oas1a, Rsad2) and lipid synthesis suppression (Scd1, Fasn), and metabolomics highlighted 193 differential metabolites (DEMs) indicative of bile acid dysregulation, glutathione redox imbalance, and amino acid metabolism anomalies. Cross-omics analysis indicated that the PPAR signaling pathway is a central regulatory hub driving lipid metabolic reprogramming and oxidative stress amplification. Furthermore, ACE2 deletion disrupted cytochrome P450-mediated detoxification and glutathione metabolism, thereby establishing a self-reinforcing oxidative injury cycle. These findings comprehensively delineate ACE2’s multifaceted role in hepatic metabolic homeostasis and provide mechanistic insights into and therapeutic targets for ACE2-associated liver diseases.
HostingRepository	PRIDE
AnnounceDate	2025-06-23
AnnouncementXML	Submission_2025-06-22_18:35:53.764.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	ji jiwoli
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-26 19:15:24	ID requested
⏵ 1	2025-06-22 18:35:54	announced

Dataset with its publication pending

submitter keyword: Angiotensin-converting Enzyme 2 (ACE2), Gene Knockout (KO), Liver Metabolic Dysregulation

Shuai Xiao
contact affiliation	Jining First People's Hospital Affiliated to Shandong First Medical University
contact email	sean.xiaoshuai@hotmail.com
lab head
ji jiwoli
contact affiliation	a342824050@gmail.com
contact email	a342824050@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/06/PXD063359

PRIDE project URI

• PRIDE
  1. PXD063359
     1. Label: PRIDE project
     2. Name: Integrated multi-omics analysis of liver metabolic dysregulation in ACE2 knockout mice