PT - JOURNAL ARTICLE AU - Benjamin Strobel AU - Germán Leparc AU - Bärbel Lämmle AU - Tobias Hildebrandt AU - Birgit Stierstorfer AU - Thorsten Lamla AU - Sebastian Kreuz TI - AAV-<em>Tgfb1</em> vs. bleomycin: Analysis of gene expression profiles in two models of pulmonary fibrosis DP - 2014 Sep 01 TA - European Respiratory Journal PG - 404 VI - 44 IP - Suppl 58 4099 - http://erj.ersjournals.com/content/44/Suppl_58/404.short 4100 - http://erj.ersjournals.com/content/44/Suppl_58/404.full SO - Eur Respir J2014 Sep 01; 44 AB - Translating clinically relevant disease mechanisms into early preclinical research is key for the successful development of new pharmaceutical drugs. For pathway-focused studies, viral vector-mediated overexpression or knockdown prove very useful to modulate target gene function in vivo. Particularly, Adenovirus (Ad) vectors have been used to set up respiratory disease models. However, even improved Ad vectors induce substantial inflammation following application into the lung, possibly interfering with disease-relevant pathways and therefore limiting their use.To identify an efficient alternative vector with the lowest possible immunogenicity, we carried out a systematic comparison of a commonly used Ad5 vector and an Adeno-associated virus (AAV) 6-based vector. While the Ad5 vector induced an inflammatory response including T-cell activation, the AAV vector did not cause any measurable immune response. We then successfully applied this AAV vector to establish a pulmonary fibrosis model in mice by overexpression of Tgfb1. Characterization based on immune cell analysis, histology and lung function measurement confirmed fibrosis manifestation. For in-depth analysis of fibrosis development over time, we applied deep sequencing to profile changes in gene expression, particularly in comparison to the commonly used bleomycin model. The increased understanding of the molecular pathways involved will help to decide in the future, which of the models is appropriate to answer defined scientific questions in pulmonary fibrosis research and preclinical drug development.