title: High-Mobility Group Box-1 Protein Disrupts Alveolar Elastogenesis of Hyperoxia-Injured Newborn Lungs.
abstract: Although high-mobility group box-1 (HMGB1) levels in tracheal aspirates are associated with the pathological features of bronchopulmonary dysplasia (BPD), the role of HMGB1 in the terminal stage of abnormal alveologenesis has not yet been understood. In this study, we addressed the role of HMGB1 in the elastogenesis disruption in the lungs of newborn mice with BPD. We found that elevations of whole lung HMGB1 level were associated with impaired alveolar development and aberrant elastin production in 85% O2-exposed lungs. HMGB1 neutralizing antibody attenuated the structural disintegration developed in hyperoxia-damaged lungs. Furthermore, HMGB1 inhibition rescued the neutrophil influx in hyperoxia-injured lung and partially abolished the mRNA level of the proinflammatory mediators, interleukin (IL)-1β and transforming growth factor (TGF)-β1. These data suggested that pulmonary HMGB1 plays an important role in the disruption of elastogenesis in the terminal stage of lung development through reduced pulmonary inflammatory response.
authors.affiliation: 1 Department of Neonatology, Children's Hospital of Chongqing Medical University , Chongqing, P.R. China .|2 Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University , Chongqing, P.R. China .
authors.forename: Benli
authors.initials: B
authors.lastname: Yu
authors.affiliation: 1 Department of Neonatology, Children's Hospital of Chongqing Medical University , Chongqing, P.R. China .|2 Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University , Chongqing, P.R. China .
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.affiliation: 1 Department of Neonatology, Children's Hospital of Chongqing Medical University , Chongqing, P.R. China .|2 Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University , Chongqing, P.R. China .
authors.forename: Qiufeng
authors.initials: Q
authors.lastname: Wan
authors.affiliation: 1 Department of Neonatology, Children's Hospital of Chongqing Medical University , Chongqing, P.R. China .|3 Department of Pharmacology, Chongqing Medical University , Chongqing, P.R. China .
authors.forename: Wenli
authors.initials: W
authors.lastname: Han
authors.affiliation: 1 Department of Neonatology, Children's Hospital of Chongqing Medical University , Chongqing, P.R. China .|2 Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University , Chongqing, P.R. China .
authors.forename: Chun
authors.initials: C
authors.lastname: Deng
authors.affiliation: 1 Department of Neonatology, Children's Hospital of Chongqing Medical University , Chongqing, P.R. China .|2 Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University , Chongqing, P.R. China .|4 Department of Hepatology and Liver Transplantation Center, Children's Hospital of Chongqing Medical University , Chongqing, P.R. China .
authors.forename: Chunbao
authors.initials: C
authors.lastname: Guo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001997:Bronchopulmonary Dysplasia / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004549:Elastin / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018496:Hyperoxia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000633:toxicity; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D053773:Transforming Growth Factor beta1; D004549:Elastin; D010100:Oxygen