title: Aberrant elastin remodeling in the lungs of O₂-exposed newborn mice; primarily results from perturbed interaction between integrins and elastin.
abstract: 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.
authors.affiliation: Department of Neonatology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Medical University, Chongqing, China.|Department of Pharmacology, Chongqing Medical University, Chongqing, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Hepatology and Liver transplantation Center, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Medical University, Chongqing, China.
authors.forename: Chunbao
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Neonatology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Medical University, Chongqing, China.
authors.forename: Qiutong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neonatology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Medical University, Chongqing, China.
authors.forename: Benli
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Neonatology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Medical University, Chongqing, China.
authors.forename: Zhaoyun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Chongqing Medical University, Chongqing, China. junqingyang01@163.com.
authors.forename: Junqing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Neonatology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Medical University, Chongqing, China. dengchun@cqmu.edu.cn.
authors.forename: Chun
authors.initials: C
authors.lastname: Deng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004549:Elastin / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D018496:Hyperoxia / Q000473:pathology; D039564:Integrin alphaV / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014333:Tropoelastin / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; C120769:Fbln5 protein, mouse; D039564:Integrin alphaV; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D014333:Tropoelastin; D004549:Elastin; D010100:Oxygen