PXD025712

PXD025712 is an original dataset announced via ProteomeXchange.

Title	Spatial resolution of proteomic changes in lung tissue from a flexible AAV-DTR/DT mouse model of acute cell deletion mimicking epithelial lung injury
Description	Lung epithelial injury leads to different pathologies, all associated with severe outcome and increased mortality. These pathologies are divided into chronic and acute diseases like idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD) or the acute lung distress syndrome (ARDS). Hallmarks of both groups of lung diseases are a breakdown of the epithelial barrier and impairment of lung function. Repeated epithelial injury leads to chronic inflammation, fibroblast activation and ultimately to scarring and stiffening of the lung. The observed decline in lung function is the first symptom of IPF patients. As these changes are occurring slowly over time, patients only present to clinicians at a rather late stage. Therefore, disease driving mechanisms can only be estimated based on observed changes in biomarkers, the transcriptome or proteome. However, alterations in signalling pathways at a very early stage of disease development can only be investigated in vitro or in animal models. In this study a novel and flexible DTR/DT model of acute epithelial lung injury driven by AAV6.2 mediated human diphtheria toxin receptor (hDTR) expression was developed and characterized. The hDTR is sensitive for diphtheria toxin (DT), thereby inducing apoptosis by blocking protein synthesis. In contrast, a polymorphism of the murine DTR protects mice from DT mediated toxicity. The AAV6.2 variant transduces specifically into bronchial epithelial and alveolar epithelial type II cells leading to their depletion after DT administration. Using laser-capture microdissection different epithelial cell regions (bronchial epithelium and alveolar epithelium) were isolated from formalin-fixed and paraffin-embedded lung tissue of AAV-stuffer and AAV-hDTR mice, which were administered intratracheally with 100 ng DT for 24 h, and analyzed using mass spectrometry.
HostingRepository	PRIDE
AnnounceDate	2022-06-30
AnnouncementXML	Submission_2022-06-30_12:33:49.839.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eva Griesser
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-29 07:04:55	ID requested
⏵ 1	2022-06-30 12:33:50	announced

Griesser E, Sch, ö, nberger T, Stierstorfer B, Wyatt H, Rist W, Lamla T, Thomas MJ, Lamb D, Geillinger-K, ä, stle K, Characterization of a flexible AAV-DTR/DT mouse model of acute epithelial lung injury. Am J Physiol Lung Cell Mol Physiol, 323(2):L206-L218(2022) [pubmed]

submitter keyword: FFPE, laser-capture microdissection, TMT, AAV, diphtheria toxin, DTR, epithelial cells

Kerstin Geillinger-Kaestle
contact affiliation	Lung Repair & Regeneration Department, Boehringer Ingelheim Pharma GmbH & Co. KG
contact email	kerstin.geillinger-kaestle@boehringer-ingelheim.com
lab head
Eva Griesser
contact affiliation	Boehringer Ingelheim Pharma GmbH & Co. KG
contact email	eva.griesser@boehringer-ingelheim.com
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/2022/06/PXD025712

PRIDE project URI

• PRIDE
  1. PXD025712
     1. Label: PRIDE project
     2. Name: Spatial resolution of proteomic changes in lung tissue from a flexible AAV-DTR/DT mouse model of acute cell deletion mimicking epithelial lung injury