PXD025821

PXD025821 is an original dataset announced via ProteomeXchange.

Title	Bi-directional epithelial-mesenchymal crosstalk provides self-sustaining pro-fibrotic signals in pulmonary fibrosis
Description	Idiopathic pulmonary fibrosis (IPF) is the prototypic progressive fibrotic lung disease with a median survival of 2-4 years. Injury to and/or dysfunction of alveolar epithelium are strongly implicated in IPF disease initiation, but what factors determine why fibrosis progresses rather than normal tissue repair occurs remain poorly understood. We previously demonstrated that ZEB1-mediated epithelial-mesenchymal transition (EMT) in human alveolar epithelial type II (ATII) cells augments TGF-β-induced profibrogenic responses in underlying lung fibroblasts by paracrine signalling. Here we investigated bi-directional epithelial-mesenchymal crosstalk and its potential to drive fibrosis progression. RNA sequencing (RNA-seq) of lung fibroblasts exposed to conditioned media from ATII cells undergoing RAS-induced EMT identified many differentially expressed genes including those involved in cell migration and extracellular matrix (ECM) regulation. We confirmed that paracrine signalling between AS-activated ATII cells and fibroblasts augmented fibroblast recruitment and demonstrated that this involved a ZEB1-tissue plasminogen activator (tPA) axis. In a reciprocal fashion, paracrine signalling from TGF-β-activated lung fibroblasts or IPF fibroblasts induced RAS activation in ATII cells, at least partially via the secreted protein, SPARC. Together these data identify that aberrant bi-directional epithelial-mesenchymal crosstalk in IPF drives a chronic feedback loop that maintains a wound-healing phenotype and provides self-sustaining pro-fibrotic signals.
HostingRepository	PRIDE
AnnounceDate	2021-08-19
AnnouncementXML	Submission_2021-08-19_04:48:09.815.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Paul Skipp
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-05 22:46:09	ID requested
⏵ 1	2021-08-19 04:48:10	announced

Dataset with its publication pending

submitter keyword: TGF-β, RAS,secretome, Proteomics

Paul James Skipp
contact affiliation	Centre for Proteomic Research, University of Southampton
contact email	pjss@soton.ac.uk
lab head
Paul Skipp
contact affiliation	Centre for Proteomic Research, University of Southampton
contact email	pjss@soton.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025821
     1. Label: PRIDE project
     2. Name: Bi-directional epithelial-mesenchymal crosstalk provides self-sustaining pro-fibrotic signals in pulmonary fibrosis