GSE173523
Transcriptomic and proteomic profiling of young and old mice in the Bleo model
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.  Therefore, we here compared young (3 months) and old mice (21 months) 21 days after intratracheal bleomycin instillation. Analyzing lung transcriptomics (mRNAs & miRNAs) and proteomics, we found most pathways to be similarly regulated in young and old mice. However, old mice show an 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 as well as it turned human healthy individuals better into “IPF patients” using an approach termed predictive disease modelling.   Comprising, young and old animals show similarly molecular hallmarks of IPF. Additionally, old mice resemble several features associated with IPF more closely compared to young animals. Overall design: Male mice were randomized before the study. Mice were instilled intratracheally (i.t.) under 3-4% isoflurane anesthesia once on day 0. Bleomycin administration was performed in a hanging position with a Vasofix-Braunüle 22G (B.Braun, Melsungen, Germany). Mice were instilled using 0.7 and 0.63 mg/kg of bleomycin sulphate (Merck, Darmstadt, Germany) in saline solution for the young and old mice, respectively. Control mice received saline solution only. Mice were analyzed 21 days after bleomycin administration.