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

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...

Full description

Saved in:
Bibliographic Details
Published in:American journal of physiology. Lung cellular and molecular physiology 2023-03, Vol.324 (3), p.L245-L258
Main Authors: Klee, Stephan, Picart-Armada, Sergio, Wenger, Kathrin, Birk, Gerald, Quast, Karsten, Veyel, Daniel, Rist, Wolfgang, Violet, Coralie, Luippold, Andreas, Haslinger, Christian, Thomas, Matthew, Fernandez-Albert, Francesc, Kästle, Marc
Format: Article
Language:English
Subjects:
Animals
Bleomycin
Bleomycin - pharmacology
Disease Models, Animal
Fibrosis
Homeostasis
Humans
Idiopathic Pulmonary Fibrosis - pathology
In vivo methods and tests
Inflammation
Interferon
Lung - metabolism
Lung diseases
Lungs
Mice
Mice, Inbred C57BL
Pathogenesis
Proteomics
Trachea
Transcriptome
Transcriptomics
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 important role in the pathogenesis of lung fibrosis. Therefore, we compared young (3 months) and old mice (21 months) 21 days after intratracheal bleomycin instillation. Analyzing lung transcriptomics (mRNAs and miRNAs) and proteomics, we found most pathways to be similarly regulated in young and old mice. However, old mice show imbalanced protein homeostasis as well as an increased inflammatory state in the fibrotic phase compared to young mice. Comparisons with published human transcriptomic data sets (GSE47460, GSE32537, and GSE24206) revealed that the gene signature of old animals correlates significantly better with IPF patients, and it also turned human healthy individuals better into "IPF patients" using an approach based on predictive disease modeling. Both young and old animals show similar molecular hallmarks of IPF in the bleomycin-induced lung fibrosis model, although old mice more closely resemble several features associated with IPF in comparison to young animals.
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00253.2021