TY - JOUR T1 - The role of transglutaminase 2 in normal and aberrant late lung development JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.OA505 VL - 48 IS - suppl 60 SP - OA505 AU - Ivana Mizikova AU - Diogo Silva AU - Werner Seeger AU - Rory Morty Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/OA505.abstract N2 - A disturbed extracellular matrix (ECM) is a feature of bronchopulmonary dysplasia (BPD). How the ECM structures are malformed is not understood. Transglutaminases are ECM cross-linking enzymes, and transglutaminase 2 (Tgm2) is deregulated in experimental and clinical BPD. No role for Tgm2 in lung development has been demonstrated. We hypothesized that Tgm2 plays a role in lung alveolarization. To address this, we employed Tgm2-/- mice in a hyperoxia-based experimental animal model of BPD.Normoxia (21% O2)-exposed Tgm2-/- mice exhibited a decreased body mass (4.98 g vs. 5.51 g; P<0.0001) and lung volume (0.23 cm3 vs. 0.27 cm3; P=0.0022) at postnatal day (P)14.5 compared to normoxia-exposed controls. Changes in lung structure were detected comparing the two groups, suggesting an arrest in alveolarization in Tgm2-/- mice. Total surface area (163.9 cm2 vs. 201.7 cm2; P=0.0155), septal thickness (10.36 µm vs. 8.45 µm; P=0.0142) and total alveoli number (3.253 x 106 vs. 4.067 x 106; P=0.0541) were perturbed in Tgm2-/- mice. Expression levels of Tgm2 were increased by hyperoxia exposure. Total surface area (124.2 cm2 vs. 201.7 cm2; P< 0.0001), MLI (61.91 µm vs. 31.73 µm; P<0.0001), septal thickness (10.27 µm vs. 8.45 µm; P=0.693) and total alveoli number (1.536 x 106 vs. 4.067 x 106; P<0.0001) were markedly altered upon hyperoxia-exposure in wild-type animals at P14.5.Tgm2 expression was upregulated by hyperoxia-expsoure in developing mouse lungs, however, genetic abrogation of Tgm2 expression was not protective. These data indicate that Tgm2 most likely plays a role in normal lung alveolarization, but does not contribute to the aberrant alveolarization seen in hyperoxia-exposed developing mouse lungs. ER -