PXD039830-1

PXD039830 is an original dataset announced via ProteomeXchange.

Title	Quantitative proteomics and RNA-sequencing of mouse liver endothelial cells identify novel regulators of BMP6 by iron
Description	Iron induces hepcidin by activating bone morphogenetic protein (BMP)6-SMAD signaling. Liver endothelial cells (LECs) produce BMP6, but the molecular mechanisms are incompletely understood. To address this, we performed proteomics and RNA-sequencing on LECs from iron-adequate and iron-loaded mice. Gene set enrichment analysis identified transcription factors activated by high iron, including Nrf-2, which was previously reported to contribute to BMP6 regulation, and proto-oncogene c-Jun (encoded by Jun). Jun knockdown blocked Bmp6, but not Nrf-2 pathway, induction by iron in LEC cultures. Moreover, chromatin immunoprecipitation of mouse livers showed iron-dependent c-Jun binding to predicted sites in Bmp6 regulatory regions. Finally, c-Jun inhibitor blunted induction of Bmp6 and hepcidin, but not Nrf-2 activity, in iron-loaded mice. However, Bmp6 expression and iron parameters were unchanged in endothelial Jun knockout mice. Our data suggest that c-Jun participates in iron-mediated BMP6 regulation independent of Nrf-2, though the mechanisms may be redundant and/or multifactorial.
HostingRepository	PRIDE
AnnounceDate	2023-12-28
AnnouncementXML	Submission_2023-12-28_11:04:42.112.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joao Paulo
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-03 06:03:30	ID requested
⏵ 1	2023-12-28 11:04:42	announced

Dataset with its publication pending

submitter keyword: Iron homeostasis, endothelial cells, liver, c-Jun, bone morphogenetic proteins

Jodie L Babitt
contact affiliation	Nephrology Division and Endocrine Unit Massachusetts General Hospital Harvard Medical School Boston, MA
contact email	Babitt.jodie@mgh.harvard.edu
lab head
Joao Paulo
contact affiliation	Harvard Medical School
contact email	joao_paulo@post.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD039830
     1. Label: PRIDE project
     2. Name: Quantitative proteomics and RNA-sequencing of mouse liver endothelial cells identify novel regulators of BMP6 by iron