PXD058023

PXD058023 is an original dataset announced via ProteomeXchange.

Title	Protein lactylation promotes AKI–CKD transition in mice
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.
HostingRepository	PRIDE
AnnounceDate	2025-07-07
AnnouncementXML	Submission_2025-07-06_19:15:45.134.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	kehong chen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-18 22:06:15	ID requested
⏵ 1	2025-07-06 19:15:45	announced

Dataset with its publication pending

submitter keyword: Mouse

kidney

LC-MSMS

lactylation

Kehong Chen
contact affiliation	Department of Nephrology, Daping hospital, Army Medical Center, Army Medical University, Chongqing, China
contact email	chenkehong@foxmail.com
lab head
kehong chen
contact affiliation	Department of Nephrology, Daping hospital, Army Medical Center, Army Medical University
contact email	chenkh@tmmu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD058023
     1. Label: PRIDE project
     2. Name: Protein lactylation promotes AKI–CKD transition in mice