PXD056805

PXD056805 is an original dataset announced via ProteomeXchange.

Title	H3K14la drives endothelial dysfunction in sepsis-induced ARDS via promoting SLC40A1/TFR-mediated ferroptosis
Description	Background: Pulmonary endothelial cell (EC) activation is a key factor in acute respiratory distress syndrome (ARDS). In sepsis, increased glycolysis leads to lactate buildup, which induces lysine lactylation (Kla) on histones and other proteins. However, the role of protein lactylation in EC dysfunction during sepsis-induced ARDS remains unclear. Methods: Integrative lactylome and proteome analysis was performed to identify the global lactylome profiling in lung tissues of septic mice. Cut&Tag analysis were used to identify the transcriptional targets of histone H3 lysine 14 lactylation (H3K14la) in ECs. Results: Septic mice exhibited elevated levels of lactate and H3K14la in lung tissues, particularly in pulmonary ECs. Suppressing glycolysis reduced both H3K14la and EC activation, suggesting a link between glycolysis and lactylation. Moreover, H3K14la was found to be enriched at promoter regions of ferroptosis-related genes such as transferrin receptor (TFRC) and solute carrier family 40 member 1 (SLC40A1), which contributed to EC activation and lung injury under septic conditions. Conclusions: We for the first time reported the role of lactate-dependent H3K14 lactylation in regulating EC ferroptosis to promote vascular dysfunction during sepsis-induced lung injury. Our findings suggest that manipulation of glycolysis/H3K14la/ferroptosis axis may provide novel therapeutic approaches for sepsis-associated ARDS.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_03:28:24.116.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Erzhen 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	2024-10-15 00:47:58	ID requested
⏵ 1	2025-05-07 03:28:24	announced

10.1002/mco2.70049;

Gong F, Zheng X, Xu W, Xie R, Liu W, Pei L, Zhong M, Shi W, Qu H, Mao E, Yang Z, Li R, Chen E, Chen Y, H3K14la drives endothelial dysfunction in sepsis-induced ARDS by promoting SLC40A1/transferrin-mediated ferroptosis. MedComm (2020), 6(2):e70049(2025) [pubmed]

submitter keyword: lactylation

ferroptosis

endothelial dysfunction

sepsis

lung injury

Erzhen Chen
contact affiliation	1 Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
contact email	rjchenerzhen@163.com
lab head
Erzhen Chen
contact affiliation	Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
contact email	rjchenerzhen@163.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056805
     1. Label: PRIDE project
     2. Name: H3K14la drives endothelial dysfunction in sepsis-induced ARDS via promoting SLC40A1/TFR-mediated ferroptosis