PXD078736-1

PXD078736 is an original dataset announced via ProteomeXchange.

Title	HK-2 cells 4D label quantitative lactylproteomic analysis
Description	Following acute kidney injury (AKI), a substantial subset of patients experiences an irreversible progression to chronic kidney disease (CKD), yet the molecular determinants governing this maladaptive transition remain elusive, and effective clinical interventions are lacking. Here, we identify lactate as a key metabolic determinant orchestrating the transition from AKI to CKD. Analysis of the UK Biobank cohort reveals that elevated circulating lactate independently predicts CKD development in AKI patients and correlates with fibrotic progression. Using murine ischemia-reperfusion injury models, we demonstrate that lactate drives sustained renal damage through post-translational lactylation of the RNA helicase DDX18. Mechanistically, p300-mediated lactylation of DDX18 at lysine 116 disrupts its nucleolar retention, causing redistribution to the nucleoplasm where it acquires enhanced binding affinity for CD44 mRNA. This subcellular relocalization stabilizes CD44 mRNA through altered RNA-protein interactions, thereby amplifying fibrotic signaling pathways. Therapeutically, we developed a kidney-targeted, cell-penetrating peptide that specifically inhibits DDX18 K116 lactylation, effectively attenuating fibrotic progression in injured kidneys. Our findings establish protein lactylation as a novel regulatory mechanism governing RNA helicase nucleolar localization and subsequent control of mRNA stability, revealing a therapeutic target for interrupting fibrotic processes in chronic kidney disease.
HostingRepository	PRIDE
AnnounceDate	2026-07-18
AnnouncementXML	Submission_2026-07-18_02:09:19.508.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lijun Dong
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	lactic acid
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-22 07:30:51	ID requested
⏵ 1	2026-07-18 02:09:20	announced

Dataset with its publication pending

submitter keyword: human

lactylation

Daming Zuo
contact affiliation	School of Laboratory Medicine and Biotechnology, Southern Medical University
contact email	zdaming@smu.edu.cn
lab head
Lijun Dong
contact affiliation	Nanfang hospital, Southern Medical University
contact email	843532936@qq.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/2026/07/PXD078736

PRIDE project URI

• PRIDE
  1. PXD078736
     1. Label: PRIDE project
     2. Name: HK-2 cells 4D label quantitative lactylproteomic analysis