Source: International Congress 2014 – Novel approaches in transcriptomics and epigenomics in inflammatory lung diseases and lung cancer
Disease area: Interstitial lung diseases

Abstract

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.

Rating:

Share or cite this content

Citations should be made in the following way:
B. Strobel, G. Leparc, B. Lämmle, T. Hildebrandt, B. Stierstorfer, T. Lamla, S. Kreuz (Biberach/Riss, Germany). AAV-Tgfb1 vs. bleomycin: Analysis of gene expression profiles in two models of pulmonary fibrosis. Eur Respir J 2014; 44: Suppl. 58, 404

Member's Comments

No comment yet.

Related content which might interest you: Metabolomic profiling of the lung in a murine model of emphysema Source: International Congress 2014 – Basic and translational research in asthma and COPD Year: 2014 Mitochondrial tRNA gene mutations in patients with idiopathic pulmonary fibrosis (IPF) and sarcoidosis Source: International Congress 2014 – Basic and translational research in lung cancer and non-neoplastic pulmonary diseases Year: 2014 Molecular mechanisms of pirfenidone activity in human lung fibroblasts Source: International Congress 2014 – Basic and translational research in lung cancer and non-neoplastic pulmonary diseases Year: 2014 Immunoproteasome expression in pulmonary fibrosis Source: Annual Congress 2013 –Cell signalling and inflammation: what's new in 2013? Year: 2013 Specialized-proresolving mediators and trancriptomic signatures in bleomycin-induced lung fibrosis Source: International Congress 2016 – Common mechanisms in lung development and fibrosis Year: 2016 Temporal profile of metaloproteases gene expression in elastase-induced emphysema Source: Annual Congress 2013 –Novel mechanisms in lung injury Year: 2013 Influenza infection affects the degree of fibrosis and apoptosis in the bleomycin mouse model Source: Annual Congress 2013 –Interesting research questions Year: 2013 Analysis of candidate genes of phenotypic expression in idiopathic pulmonary fibrosis Source: International Congress 2014 – ILDs 5 Year: 2014 Comparison of expression of napsin A and surfactant protein D in bleomycin-induced pulmonary fibrosis mouse model Source: Annual Congress 2013 –Diffuse parenchymal lung disease I Year: 2013 Discovery and validation of peripheral blood gene expression profiles predictive of poor outcome and disease progression in idiopathic pulmonary fibrosis Source: International Congress 2014 – Pathogenetic mechanisms in pulmonary fibrosis Year: 2014 Loss of CARM1 prolongs bleomycin-induced pulmonary fibrosis Source: International Congress 2014 – Animal models: asthma, COPD and beyond Year: 2014 The immunomodulatory effect of protein S in pulmonary fibrosis Source: Annual Congress 2013 –Diffuse pulmonary fibrosis Year: 2013 Pre-clinical evaluation of a novel and selective PI3K δ/gamma inhibitor in pulmonary fibrosis Source: International Congress 2014 – New treatments for cough, asthma, COPD and ILDs Year: 2014 Role of microRNA 17/92 cluster and microRNA 21 in the pathogenesis of pulmonary hypertension – Novel therapeutic targets Source: Annual Congress 2013 –Pulmonary circulation: basic science Year: 2013 Pulmonary distribution and localization of pirfenidone in animal models of IPF by MS/MS Source: International Congress 2014 – ILDs 4 Year: 2014 A mechanism for acceleration of GM-CSF autoantibody (GMAb) production in autoimmune pulmonary alveolar proteinosis (aPAP) Source: International Congress 2014 – Molecular pathogenesis of pulmonary inflammatory diseases (COPD, asthma and ILD) Year: 2014 Systemic inflammatory response to smoking in chronic obstructive pulmonary disease: Evidence of a gender effect Source: International Congress 2014 – Basic and translational research in asthma and COPD Year: 2014 Interaction between mitochondrial ROS and ER stress on PHMG-induced pulmonary fibrosis Source: International Congress 2016 – ILD: from the bench to the bedside Year: 2016 Characterization of a new rat model of heritable PAH Source: International Congress 2016 – Pulmonary hypertension: novel insights Year: 2016 Differential lipopolysaccharide-induced gene expression profile in peripheral blood mononuclear cells of patients with severe asthma and chronic obstructive pulmonary disease Source: International Congress 2014 – Basic and translational research in asthma and COPD Year: 2014