epsilon-(gamma-glutamyl)-lysine and Bronchopulmonary-Dysplasia

The generation, maturation and remodelling of the extracellular matrix (ECM) are essential for the formation of alveoli during lung development. Alveoli formation is disturbed in preterm infants that develop bronchopulmonary dysplasia (BPD), where collagen fibres are malformed, and perturbations to lung ECM structures may underlie BPD pathogenesis. Malformed ECM structures might result from abnormal protein cross-linking, in part attributable to the increased expression and activity of transglutaminase 2 (TGM2) that have been noted in affected patient lungs, as well as in hyperoxia-based BPD animal models. The objective of the present study was to assess whether TGM2 plays a causal role in normal and aberrant lung alveolarization. Targeted deletion of Tgm2 in C57BL/6J mice increased septal thickness and reduced gas-exchange surface area in otherwise normally developing lungs. During aberrant lung alveolarization that occurred under hyperoxic conditions, collagen structures in Tgm2

Topics: Animals; Bronchopulmonary Dysplasia; Collagen; Cysteamine; Dipeptides; Disease Models, Animal; Extracellular Matrix; Female; Gene Expression Regulation, Developmental; Gene Expression Regulation, Enzymologic; GTP-Binding Proteins; Hyperoxia; Lung; Mice, Inbred C57BL; Mice, Knockout; Molecular Targeted Therapy; Protein Glutamine gamma Glutamyltransferase 2; Pulmonary Alveoli; Transglutaminases