PXD041444

PXD041444 is an original dataset announced via ProteomeXchange.

Title	The endoplasmic reticulum stress sensor IRE1 regulates collagen secretion through the enforcement of the proteostasis factor P4HB contributing to liver damage and fibrosis
Description	Collagen is the most abundant protein in the cell and the main cargo of the secretory pathway, contributing to hepatic fibrogenesis due to extensive deposition of extracellular matrix (ECM). Here we investigated the possible contribution of the unfolded protein response (UPR), the main adaptive pathway that monitors and adjusts the protein production capacity at the endoplasmic reticulum (ER), to collagen biogenesis and liver disease. Genetic ablation of the ER stress sensor IRE1 reduced liver damage and diminished collagen deposition in models of liver fibrosis triggered by carbon tetrachloride (CCl4) administration or by high fat diet. Proteomic profiling identified the prolyl 4-hydroxylase (P4HB, also known as PDIA1), as a major IRE1-regulated gene, a critical factor involved in collagen maturation. Cell culture studies demonstrated that IRE1 deficiency results in collagen retention at the ER and altered secretion, a phenotype rescued by P4HB overexpression. Taken together, our results collectively establish a role of the IRE1/P4HB in the regulation of collagen production and its role in the pathogenesis of various disease states.
HostingRepository	PRIDE
AnnounceDate	2025-05-17
AnnouncementXML	Submission_2025-05-17_05:59:11.232.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Valeria Garcia
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-10 17:47:08	ID requested
⏵ 1	2025-05-17 05:59:11	announced

10.1097/HEP.0000000000001335;

submitter keyword: IRE1,collagen, UPR, liver fibrosis, PDIA1/ P4HB

Lars Plate
contact affiliation	Vanderbilt University
contact email	lars.plate@vanderbilt.edu
lab head
Valeria Garcia
contact affiliation	Vanderbilt University
contact email	valeria.a.garcia.lopez@vanderbilt.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041444
     1. Label: PRIDE project
     2. Name: The endoplasmic reticulum stress sensor IRE1 regulates collagen secretion through the enforcement of the proteostasis factor P4HB contributing to liver damage and fibrosis