PXD032723

PXD032723 is an original dataset announced via ProteomeXchange.

Title	Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism
Description	Chronic inflammation underpins many human diseases. The morbidity and mortality of chronic inflammation is often mediated through metabolic dysfunction. Inflammatory and metabolic processes vary through circadian time, suggesting an important temporal crosstalk between these systems. Using an established mouse model of rheumatoid arthritis, here we show thatchronic inflammatory arthritis results in rhythmic joint inflammation and drives major changes in muscle and liver energy metabolism and rhythmic gene expression. Transcriptional and phosphoproteomic analyses reveal alteration in lipid metabolism and mitochondrial function associated with increased EGFR-JAK11 STAT3 signalling. Metabolomic analyses confirmed rhythmic metabolic rewiring with impaired β-oxidation and lipid handling, and revealed a pronounced shunt towards sphingolipid and ceramide accumulation. The arthritis-related production of ceramides was most pronounced during the day, the time of peak inflammation and increased reliance on fatty acid oxidation. Thus, our data demonstrate that localised joint inflammation drives a time-of-day dependent build-up of bioactive lipid species driven by rhythmic inflammation and altered EGFR-STAT signalling.
HostingRepository	PRIDE
AnnounceDate	2022-05-08
AnnouncementXML	Submission_2022-05-08_05:35:52.529.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Roman Fischer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-23 06:09:44	ID requested
1	2022-05-08 04:19:46	announced
⏵ 2	2022-05-08 05:35:53	announced	2022-05-08: Updated publication reference for PubMed record(s): 35482925.

Downton P, Sanna F, Maidstone R, Poolman TM, Hayter EA, Dickson SH, Ciccone NA, Early JO, Adamson A, Spiller DG, Simpkins DA, Baxter M, Fischer R, Rattray M, Loudon ASI, Gibbs JE, Bechtold DA, Ray DW, Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism. Proc Natl Acad Sci U S A, 119(18):e2112781119(2022) [pubmed]

submitter keyword: Rheumatoid arthritis, inflammation, circadian clock, mitochondria, ceramide

Roman Fischer
contact affiliation	Discovery Proteomics Facility Target Discovery Institute University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
lab head
Roman Fischer
contact affiliation	University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
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/2022/05/PXD032723

PRIDE project URI

• PRIDE
  1. PXD032723
     1. Label: PRIDE project
     2. Name: Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism