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PXD025712

PXD025712 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSpatial resolution of proteomic changes in lung tissue from a flexible AAV-DTR/DT mouse model of acute cell deletion mimicking epithelial lung injury
DescriptionLung 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.
HostingRepositoryPRIDE
AnnounceDate2022-06-30
AnnouncementXMLSubmission_2022-06-30_12:33:49.839.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEva Griesser
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-04-29 07:04:55ID requested
12022-06-30 12:33:50announced
Publication List
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]
Keyword List
submitter keyword: FFPE, laser-capture microdissection, TMT, AAV, diphtheria toxin, DTR, epithelial cells
Contact List
Kerstin Geillinger-Kaestle
contact affiliationLung Repair & Regeneration Department, Boehringer Ingelheim Pharma GmbH & Co. KG
contact emailkerstin.geillinger-kaestle@boehringer-ingelheim.com
lab head
Eva Griesser
contact affiliationBoehringer Ingelheim Pharma GmbH & Co. KG
contact emaileva.griesser@boehringer-ingelheim.com
dataset submitter
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