Elevated Wnt–Related Tracheal Aspirate Proteins LEF‐1 and ‐βcatenin Predicts the Development of Bronchopulmonary Dysplasia in Very‐Low‐Birth‐Weight Infants

Abstract

Taking a basic biologic approach, and using a wide range of models, we have demonstrated alveolar interstitial fibroblast‐to‐myofibroblast transdifferentiation, characterized by the down‐regulation of Parathyroid Hormone‐related Protein (PTHrP) signaling, and up‐regulation of Wnt signaling as a key event in the pathogenesis of Bronchopulmonary Dysplasia (BPD). Though decreased tracheal aspirate (TA) PTHrP levels in ventilated Very‐Low‐Birth‐Weight Infants (VLBWIs) during the first wk of life predict the later development of BPD, there is no information on the levels of Wnt‐related proteins in the TA of these infants. Twenty ventilated VLBWIs (birth weight 943 ± 302 g (mean ± SD); GA 27 ± 2weeks; 10M:10F) were studied. The TAs were collected once daily during the first 3 days of life, or until extubation, whichever was earlier, and immediately frozen for subsequent analysis by ELISA and Western blot for LEF‐1 and β‐catenin, two key markers of Wnt activation. LEF‐1 and β‐catenin levels, as determined by both ELISA and Western blotting, were significantly higher in infants who continued to be ventilated at 1 wk of age, and who later went on to develop BPD, compared to infants who were extubated by 1 wk of age and did not develop BPD. We conclude that in combination with the lower TA PTHrP content, higher Wnt‐related proteins can be developed into sensitive and specific biomarkers to predict, diagnose, and monitor BPD in ventilated VLBWIs. Disclosure: Supported by grants from the NIH (HL75405, HD51857, HD058948) and the TRDRP (14RT‐0073, 15IT‐0250, 17RT‐0170).