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Aberrant elastin remodeling in the lungs of O2-exposed newborn mice; primarily results from perturbed interaction between integrins and elastin
- Han, Wenli, Guo, Chunbao, Liu, Qiutong, Yu, Benli, Liu, Zhaoyun, Yang, Junqing, Deng, Chun
- Cell and tissue research 2015 v.359 no.2 pp. 589-603
- air, bronchopulmonary dysplasia, elastin, gene expression, histology, hyperoxia, image analysis, integrins, lungs, mice, neonates, transforming growth factor beta 1
- Excessive localization of elastin from septal tips to alveolar walls is a key feature of bronchopulmonary dysplasia (BPD). The abnormal accumulation of lung elastin, involving the structural and functional interaction of a series of proteins, remains poorly understood. To further investigate the mechanisms accounting for the abnormal accumulation of elastin in the lungs of newborn mice with BPD, we evaluate elastin distribution and its interaction with proteins involved in its aberrant localization, such as integrin αv, fibulin-5 and transforming growth factor β1 (TGF-β1), in lungs of newborn mice exposed to 60 % O₂ for 21 days. Lung histology revealed aberrant elastin production and impaired lung septation in O₂-exposed lungs, while tropoelastin, integrin αv, fibulin-1, fibulin-2 and fibulin-4 gene expression were elevated. Dual staining image analysis of lung sections revealed that co-localization of integrin αv and elastin increased following O₂ exposure with elastin distributed throughout the walls of air spaces rather than at septal tips. Furthermore, integrin αv appeared to be induced initially. Concurrently, increased fibulin-5 and TGF-β1 (which may regulate elastic fiber assembly) expression was detected, which may explain the altered lung elastin deposition and defective septation that are observed during BPD. These data support the hypothesis that excessive and aberrant αv integrin expression was initially induced by hyperoxia; αv integrin then interacted with and recruited elastin. These alterations were accompanied by fibulin-5 deposition and TGF-β1 activation, which may impede normal matrix remodeling, thereby contributing to the pathological pulmonary features of BPD.