TY - JOUR T1 - A role for the accessory type III transforming growth factor β receptor (Tgfbr3) in lung alveolarisation JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.PA4026 VL - 48 IS - suppl 60 SP - PA4026 AU - Agnieszka Pozarska AU - Gero Niess AU - Werner Seeger AU - Rory Morty Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/PA4026.abstract N2 - Bronchopulmonary dysplasia (BPD) is a common complication of premature birth, characterised by arrested secondary septation. Molecular mechanisms of arrested secondary septation are not known. Members of the transforming growth factor (TGF)-β growth factor superfamily are accredited with key roles in lung development and BPD. We profiled lung expression of the TGF-β signaling machinery in mice in a hyperoxia-based BPD model, and detected a down-regulation Tgfbr3 expression. Using laser-capture microdissection, Tgfbr3 mRNA expression was reduced in both the lung vascular and parenchymal compartments in response to hyperoxia. Abrogation of Tgfbr3 expression using siRNA caused a two-fold increase in proliferation and the migration of pulmonary artery smooth muscle cells. Furthermore, knockdown of Tgfbr3 in pulmonary microvascular endothelial cells caused a decrease in endothelial tube formation. We then created a floxed Tgfbr3 (Tgfbr3fl/fl) mouse line, and used this mouse line, in combination with smooth muscle (SMMHC-CreERT2) and endothelial (Tie2-CreERT2) mouse driver lines where Cre-recombinase can be selectively induced in cells with smooth muscle properties and in endothelial cells, respectively, after tamoxifen injection. Induction of Cre-recombinase in post-natal mouse pups at post-natal day (P)1 and P2 caused a 50% decrease in alveolar number at P7 in SMMHC-CreERT2/Tgfbr3fl/fl mice, without any change in septal thickness (assessed by stereological analysis). In contrast, there was no effect noted in lung structure in Tie2-CreERT2/Tgfbr3fl/fl mice. These data implicate Tgfbr3 in cells with smooth muscle properties, as a key mediator of post-natal lung alveolarisation. ER -