ADAMTS18 Deficiency Leads to Pulmonary Hypoplasia and Bronchial Microfibril Accumulation.
iScience
; 23(9): 101472, 2020 Sep 25.
Article
em En
| MEDLINE
| ID: mdl-32882513
ABSTRACT
ADAMTSs (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 adult Adamts18-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.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
IScience
Ano de publicação:
2020
Tipo de documento:
Article