Background: The WNT/β-CATENIN signaling cascade is crucial for the patterning of the early lung morphogenesis in mice, but its role in the developing human lung remains to be determined. In this study, expression patterns of canonical WNT/β-CATENIN signaling components, including WNT ligands (WNT2, WNT7B), receptors (FZD4, FZD7, LRP5, LRP6), transducers (DVL2, DVL3, GSK-3β, β-CATENIN, APC, AXIN2), transcription factors (TCF4, LEF1) and antagonists (SOSTDC1) were examined in human embryonic lung at 7, 12, 17 and 21 weeks of gestation (W) by real-time qRT-PCR and in situ hybridization.
Results: qRT-PCR analysis showed that some of these components were gradually upregulated, while some were significantly downregulated from the 7 W to the 12 W. However, most components reached a high level at 17 W, with a subsequent decrease at 21 W. In situ hybridization showed that the canonical WNT ligands and receptors were predominantly located in the peripheral epithelium, whereas the canonical WNT signal transducers and transcription factors were not only detected in the respiratory epithelium, but some were also scattered at low levels in the surrounding mesenchyme in the developing human lung. Furthermore, Western blot, qRT-PCR and histological analysis demonstrated that the β-CATENIN-dependent WNT signaling in embryonic human lung was activated in vitro by CHIR 99021 stimulation.
Conclusions: This study of the expression patterns and in vitro activity of the canonical WNT/β-CATENIN pathways suggests that these components play an essential role in regulation of human lung development.