PXD023134

PXD023134 is an original dataset announced via ProteomeXchange.

Title	Human Neutrophils in Pulmonary Arterial Hypertension by LC-MSMS
Description	Neutrophil elastase (NE) is implicated in pulmonary arterial hypertension (PAH) but the role of neutrophils in the pathogenesis of PAH is unclear. Here we show that neutrophils from PAH vs. control subjects produce and release increased NE associated with enhanced extracellular trap formation. PAH neutrophils are highly adherent and show decreased migration consistent with increased vinculin, identified on proteomic analysis and previously linked to an antiviral response. This was substantiated by a transcriptomic interferon signature in PAH neutrophils and an increase in human endogenous retrovirus (HERV-K) envelope protein. NE and interferon genes are induced by HERV-K envelope and vinculin is increased by HERV-K dUTPase that is elevated in PAH plasma. Neutrophil exosomes from PAH plasma contain increased NE and HERV-K envelope and induce pulmonary hypertension in mice, that is mitigated by the NE inhibitor and antiviral agent, elafin. Thus elevated HERVs explain pathological neutrophils linked to PAH induction and progression.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:24:31.876.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shalina Taylor
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-15 01:41:29	ID requested
1	2023-03-10 18:16:57	announced
⏵ 2	2023-11-14 08:24:34	announced	2023-11-14: Updated project metadata.

Taylor S, Isobe S, Cao A, Contrepois K, Benayoun BA, Jiang L, Wang L, Melemenidis S, Ozen MO, Otsuki S, Shinohara T, Sweatt AJ, Kaplan J, Moonen JR, Marciano DP, Gu M, Miyagawa K, Hayes B, Sierra RG, Kupitz CJ, Del Rosario PA, Hsi A, Thompson AAR, Ariza ME, Demirci U, Zamanian RT, Haddad F, Nicolls MR, Snyder MP, Rabinovitch M, Endogenous Retroviral Elements Generate Pathologic Neutrophils in Pulmonary Arterial Hypertension. Am J Respir Crit Care Med, 206(8):1019-1034(2022) [pubmed]

submitter keyword: LC-MSMS, Pulmonary Arterial Hypertension,Neutrophils

Lihua Jiang
contact affiliation	Stanford University, Department of Genetics, United States
contact email	lihuaj@stanford.edu
lab head
Shalina Taylor
contact affiliation	Stanford University
contact email	shalina@stanford.edu
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/2023/03/PXD023134

PRIDE project URI

• PRIDE
  1. PXD023134
     1. Label: PRIDE project
     2. Name: Human Neutrophils in Pulmonary Arterial Hypertension by LC-MSMS