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Series GSE48455 Query DataSets for GSE48455
Status Public on Oct 28, 2014
Title Translation value of the bleomycin rat model for the treatment of patients with Idiopathic Pulmonary Fibrosis (IPF)
Organism Rattus norvegicus
Experiment type Expression profiling by array
Summary 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.
 
Overall design 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
 
Contributor(s) Bauer Y, Tedrow J, de Bernard S, Gibson KF, Guardella BJ, Hess P, Klenk A, Lindell KO, Renault B, Rey M, Weber E, Nayler O, Kaminski N
Citation(s) 25029475
Submission date Jul 01, 2013
Last update date Oct 29, 2014
Contact name Axel Klenk
E-mail(s) [email protected]
Organization name Idorsia Pharmaceuticals Ltd.
Department Research Informatics
Street address Hegenheimermattweg 91
City Allschwil
ZIP/Postal code 4123
Country Switzerland
 
Platforms (1)
GPL7294 Agilent-014879 Whole Rat Genome Microarray 4x44K G4131F (Probe Name version)
Samples (72)
GSM1179079 Lung of bleomycin-treated rat after 8W, replicate 4
GSM1179080 Lung of vehicle-treated rat after 3W, replicate 3
GSM1179081 Lung of bleomycin-treated rat after 3D, replicate 4
Relations
BioProject PRJNA210199

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE48455_RAW.tar 1.1 Gb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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