文章基本信息

标题：ADAMTS18 Deficiency Leads to Pulmonary Hypoplasia and Bronchial Microfibril Accumulation
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作者：Tiantian Lu ; Xiaotian Lin ; Yi-Hsuan Pan 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：9
页码：1-34
DOI：10.1016/j.isci.2020.101472
语种：English
出版社：Elsevier
摘要：SummaryADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) are secreted metalloproteinases that play a major role in the assembly and degradation of the extracellular matrix (ECM). In this study, we show that ADAMTS18, produced by the epithelial cells of distal airways and mesenchymal cells in lung apex at early embryonic stages, serves as a morphogen in lung development. ADAMTS18 deficiency leads to reduced number and length of bronchi, tipped lung apexes, and dilated alveoli. These developmental defects worsen lipopolysaccharide-induced acute lung injury and bleomycin-induced lung fibrosis in adultAdamts18-deficient mice. ADAMTS18 deficiency also causes increased levels of fibrillin1 and fibrillin2, bronchial microfibril accumulation, decreased focal adhesion kinase signaling, and disruption of F-actin organization. Our findings indicate that ECM homeostasis mediated by ADAMTS18 is pivotal in airway branching morphogenesis.Graphical AbstractDisplay OmittedHighlights•ADAMTS18 serves as a morphogen in early lung development•ADAMTS18 deficiency increases lung susceptibility to injuries•ADAMTS18 affects airway branching by regulating bronchial microfibril abundanceDevelopmental Genetics; Molecular Biology