Abstract
BACKGROUND:
We have previously shown that the Hox gene Hoxbโ5 is necessary for normal mouse lung branching morphogenesis. Abnormal Hoxbโ5 regulation causes specific alterations in airway branching. We hypothesized that Hoxbโ5 is similarly involved in human lung branching morphogenesis, and is abnormally expressed in bronchopulmonary sequestration (BPS) and congenital cystic adenomatoid malformation (CCAM), both of which are congenital lung malformations with abnormal airway development.
METHODS:
The temporal, spatial, and cellular expression of the Hoxbโ5 protein was evaluated in normal human lung and BPS and CCAM tissue using Western blot analysis and immunocytochemistry.
RESULTS:
The expression of Hoxbโ5 during human lung development showed strong similarities to that during mouse lung development. Western blots showed high Hoxbโ5 protein levels in the pseudoglandular period (PSG), decreased but sustained levels in the canalicular period (CAN), and negligible levels during the alveolar period (ALV). Immunocytochemistry showed Hoxbโ5 protein expression in mesenchymal cells around branching airways in the pseuodglandular period, subepithelial fibroblast localization (especially at airway branch points) in the CAN and minimal expression in the ALV. In BPS and CCAM tissue, Hoxbโ5 protein levels were increased compared to ageโ and developmentallyโmatched lung tissue, and were more similar to the PSG and CAN with Hoxbโ5โpositive cells in mesenchyme surrounding abnormally branched airways.
CONCLUSIONS:
Hoxbโ5 expression during human lung branching morphogenesis, which is similar to that observed in mouse lung development, indicates that it plays a role in controlling airway patterning. This notion is supported by results from BPS and CCAM tissue, in which Hoxbโ5 is maintained in a manner typical of an earlier developmental stage and is associated with development of abnormal lung tissue. Birth Defects Research (Part A), 2003. ยฉ 2003 WileyโLiss, Inc.