Dataset Information

Proteomic profiling of young and old mice in the bleomycin model

ABSTRACT: The most preclinical used in vivo model to study lung fibrosis is the bleomycin-induced lung fibrosis model in 2-3-month-old mice. Although this model resembles key aspects of idiopathic pulmonary fibrosis (IPF), there are limitations in its predictability for the human disease. One of the main differences is the juvenile age of animals that are usually used in experiments, resembling humans of around 20 years. Because IPF patients are usually older than 60 years, aging appears to play an important role in the pathogenesis of lung fibrosis. We here compared young (3 months) and old (21 months) mice 21 days after intratracheal bleomycin instillation.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Lung

SUBMITTER: Daniel Veyel

LAB HEAD: Wolfgang Rist

PROVIDER: PXD026222 | Pride | 2024-09-10

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	181022_Bleo_lung_day_21_ensemble84.msf	Msf
	181108_Annotation_file_proteomics_ensembl84.txt	Txt
	181108_proteomics_ensemble84_tic-chnl-plex-norm_filtered.txt	Txt
	20180720_lung_1_fraction_1.raw	Raw
	20180720_lung_1_fraction_2.raw	Raw

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Publications

Transcriptomic and proteomic profiling of young and old mice in the bleomycin model reveals high similarity.

Klee Stephan S Picart-Armada Sergio S Wenger Kathrin K Birk Gerald G Quast Karsten K Veyel Daniel D Rist Wolfgang W Violet Coralie C Luippold Andreas A Haslinger Christian C Thomas Matthew M Fernandez-Albert Francesc F Kästle Marc M

American journal of physiology. Lung cellular and molecular physiology 20230110 3

The most common preclinical, in vivo model to study lung fibrosis is the bleomycin-induced lung fibrosis model in 2- to 3-mo-old mice. Although this model resembles key aspects of idiopathic pulmonary fibrosis (IPF), there are limitations in its predictability for the human disease. One of the main differences is the juvenile age of animals that are commonly used in experiments, resembling humans of around 20 yr. Because IPF patients are usually older than 60 yr, aging appears to play an importa ...[more]

PMID: 36625483

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Project description:Intratracheal application of bleomycin is known to induce inflammatory and fibrotic reactions in the lung within a short period of time and histological features include infiltration of inflammatory cells, collagen deposition and obliteration of alveolar spaces. Because some of these features are found in patients with idiopathic pulmonary fibrosis (IPF), the bleomycin-induced lung fibrosis animal model is commonly used. However, exploratory treatments that were successfully used in this animal model and progressed to clinical trials lacked significant efficacy in humans. Here, the bleomycin-induced rat lung fibrosis model was studied using whole genome expression data that was collected at various time points and the relevance to human disease was evaluated through comparison with whole genome expression data from IPF patient-derived lung biopsies. The highest gene expression correlation between both species was observed in animals 7 days after bleomycin instillation. These gene expression signatures helped to identify a set of twelve novel disease-relevant translational gene markers that were able to separate IPF patients from controls. Furthermore, three Wnt/-catenin pathway-related genes that belong to this translational gene marker set showed, together with clinical diffusing capacity of the lung for carbon monoxide (DLCO) measurements, the potential to stratify IPF patients according to disease severity. Pirfenidone attenuated a subset of the translational gene markers in the bleomycin-induced fibrosis model, in particular those related to Wnt/-catenin-signaling. This novel translational gene marker panel offers improved possibilities to evaluate disease-modifying efficacy of novel therapeutic concepts in the bleomycin-induced rat lung fibrosis model and could be applied as a diagnostic and prognostic tool for IPF patient care. Comparison of bleomycin-treated and control rats after 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks and 8 weeks; 5 animals per group