A disintegrin and metalloproteinase with thrombospondin motifs 18 (ADAMTS18) is a novel regulator of BPD

Bronchopulmonary dysplasia (BPD) is seen commonly in preterm neonates. The pathogenesis of this condition remains poorly understood. ADAMTS18 is a member of ADAMTSs that has been implicated in development and various malignancies. Gene array analysis of a murine model of hyperoxic-induced BPD indicated that Admats18 is a novel gene associated with BPD, yet little is known about its actual functions in vivo. Here, we used an Adamts18 knockout (KO) mouse model to further investigate the role of ADAMTS18 in lung development and BPD progression. Adamts18 mRNA was expressed at different stages of lung development, particularly at the tips of growing bronchial branches of embryonic day (E) 14.5. Adamts18 KO mice exhibited occluded small airways, enlarged airspace, and significantly decreased radial alveolar count, leading to alveolar simplification with a reduction in the overall surface area for gas exchange. Aberrant elastin distribution and reduced pulmonary microvasculature were also seen in KO mice. Together, this first characterization of ADAMTS18 in BPD-like lung dysplasia provides new insight to diagnose or treat BPD clinically.