Link: https://www.ncbi.nlm.nih.gov/pubmed/30260286

Am J Physiol Lung Cell Mol Physiol. 2018 Sep 27. doi: 10.1152/ajplung.00148.2018. [Epub ahead of print]
Proteomic Profiling of Tracheal Fluid in an Ovine Model of Congenital Diaphragmatic Hernia and Fetal Tracheal Occlusion.
Peiro JL1, Oria M1, Aydin E1, Joshi R2, Cabanas N3, Schmidt R4, Schroeder C4, Marotta M5, Varisco BM6.
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Abstract
Congenital diaphragmatic hernia (CDH) occurs in ~1:2000 pregnancies and is associated with substantial morbidity and mortality. Fetal tracheal occlusion (TO) is an emerging therapy which improves lung growth and reduces mortality; although, substantial respiratory compromise persists in survivors. In this study, we used tracheal fluid in a fetal sheep model of CDH with TO for proteomic analysis with subsequent validation of findings in sheep lung tissue. We found that the proteomic profiles of CDH tracheal fluid was most similar to control lung and CDH/TO lung most similar to TO lung. Among 118 proteins altered in CDH, only 11 were reciprocally regulated in CDH/TO. The most significantly altered pathways and processes were cell proliferation, PI3K/AKT/mTOR signaling, inflammation, and microtubule dynamics. CDH suppressed and TO promoted cell-proliferation and AKT-related signaling cascades. By Western blot and immunohistochemistry, epithelial PCNA and phosphorylated AKT was decreased in CDH and increased in TO and CDH/TO lungs. The Wnt target Axin2 was decreased 3-fold in CDH lung compared to control without a significant increase in CDH/TO lung. Cilia-related pathways were among the most dysregulated with CDH lung having a nearly two-fold increase in acetylated α-tubulin and a relative increase in the number of ciliated cells. While TO improves lung growth and patient survival in CDH, the procedure substantially alters many processes important in lung development and cell differentiation. Further elucidation of these changes will be critical to improving lung health in infants with CDH treated with TO.