PT  - JOURNAL ARTICLE
AU  - Outi Leppäranta
AU  - Maxim Bespalov
AU  - Marjukka Myllärniemi
AU  - Katri Koli
TI  - Molecular screening – A search for potential drugs for idiopathic pulmonary fibrosis
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - p3806
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/p3806.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/p3806.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - Background: Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease with a poor prognosis and very few therapeutic options. On a molecular level, patients with IPF have increased amounts of BMP inhibitor gremlin in their lungs (BMP, bone morphogenetic protein). Gremlin decreases BMP signalling and, as a consequence, TGF-β signalling is increased (TGF-β, transforming growth factor-beta). The balance between BMP and TGF-β signalling activities in the lung is of crucial importance during e.g. regenerative processes. Thus, severe alterations in these signalling activities are likely to contribute to the pathogenesis of IPF.Aim: To use high-throughput chemical screening as an approach to find molecules which could normalize the TGF-β/BMP balance in the fibrotic lung.Methods: The screen was performed with a commercial chemical library with ca. 2000 compounds. The set-up is based on two reporter cell lines that contain either a BMP- or a TGF-β-responsive element linked to a luciferase gene. The effect of the chemicals is evaluated by measuring the changes in the expression of the luciferase gene.Results: Using this approach we have been able to identify compounds which modulate the BMP/TGF-β signalling balance in the reporter cell lines. One compound was also shown to modulate endogenous BMP/TGF-β signalling activities in lung epithelial cells.Conclusions & future directions: Using chemical compound screening it is possible to identify small-molecular weight compounds that enhance BMP signalling in lung epithelial cells. These compounds are potential drugs for the prevention of progression of IPF. Their effects will be evaluated in preclinical in vivo studies using a mouse model of pulmonary fibrosis.