Link: https://www.ncbi.nlm.nih.gov/pubmed/30278961

J Surg Res. 2018 Nov;231:411-420. doi: 10.1016/j.jss.2018.06.064. Epub 2018 Jul 14.
Fetal lung transcriptome patterns in an ex vivo compression model of diaphragmatic hernia.
Fox ZD1, Jiang G1, Ho KKY2, Walker KA1, Liu AP2, Kunisaki SM3.
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Abstract
BACKGROUND:
The purpose of this study was to employ a novel ex vivo lung model of congenital diaphragmatic hernia (CDH) to determine how a mechanical compression affects early pulmonary development.

METHODS:
Day-15 whole fetal rat lungs (n = 6-12/group) from nitrofen-exposed and normal (vehicle only) dams were explanted and cultured ex vivo in compression microdevices (0.2 or 0.4 kPa) for 16 h to mimic physiologic compression forces that occur in CDH in vivo. Lungs were evaluated with significance set at P < 0.05.

RESULTS:
Nitrofen-exposed lungs were hypoplastic and expressed lower levels of surfactant protein C at baseline. Although compression alone did not alter the α-smooth muscle actin (ACTA2) expression in normal lungs, nitrofen-exposed lungs had significantly increased ACTA2 transcripts (0.2 kPa: 2.04 ± 0.15; 0.4 kPa: 2.22 ± 0.11; both P < 0.001). Nitrofen-exposed lungs also showed further reductions in surfactant protein C expression at 0.2 and 0.4 kPa (0.53 ± 0.04, P < 0.01; 0.69 ± 0.23, P < 0.001; respectively). Whereas normal lungs exposed to 0.2 and 0.4 kPa showed significant increases in periostin (POSTN), a mechanical stress-response molecule (1.79 ± 0.10 and 2.12 ± 0.39, respectively; both P < 0.001), nitrofen-exposed lungs had a significant decrease in POSTN expression (0.4 kPa: 0.67 ± 0.15, P < 0.001), which was confirmed by immunohistochemistry.

CONCLUSIONS:
Collectively, these pilot data in a model of CDH lung hypoplasia suggest a primary aberration in response to mechanical stress within the nitrofen lung, characterized by an upregulation of ACTA2 and a downregulation in SPFTC and POSTN. This ex vivo compression system may serve as a novel research platform to better understand the mechanobiology and complex regulation of matricellular dynamics during CDH fetal lung development.

Copyright © 2018 Elsevier Inc. All rights reserved.

KEYWORDS:
Congenital diaphragmatic hernia; Lung development; Mechanical compression; Periostin; Pulmonary hypoplasia