Pulmonary transcriptome analysis in the surgically induced rabbit model of diaphragmatic hernia treated with fetal tracheal occlusion

Alexander C Engels; Paul D Brady; Molka Kammoun; Julio Finalet Ferreiro; Philip DeKoninck; Masayuki Endo; Jaan Toelen; Joris R Vermeesch; Jan Deprest

doi:10.1242/dmm.021626

Pulmonary transcriptome analysis in the surgically induced rabbit model of diaphragmatic hernia treated with fetal tracheal occlusion

Alexander C Engels, Paul D Brady, Molka Kammoun, Julio Finalet Ferreiro, Philip DeKoninck, Masayuki Endo, Jaan Toelen, Joris R Vermeesch, Jan Deprest^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

17 Citations (Scopus)

Abstract

Congenital diaphragmatic hernia (CDH) is a malformation leading to pulmonary hypoplasia, which can be treated in utero by fetal tracheal occlusion (TO). However, the changes of gene expression induced by TO remain largely unknown but could be used to further improve the clinically used prenatal treatment of this devastating malformation. Therefore, we aimed to investigate the pulmonary transcriptome changes caused by surgical induction of diaphragmatic hernia (DH) and additional TO in the fetal rabbit model. Induction of DH was associated with 378 upregulated genes compared to controls when allowing a false-discovery rate (FDR) of 0.1 and a fold change (FC) of 2. Those genes were again downregulated by consecutive TO. But DH+TO was associated with an upregulation of 157 genes compared to DH and controls. When being compared to control lungs, 106 genes were downregulated in the DH group and were not changed by TO. Therefore, the overall pattern of gene expression in DH+TO is more similar to the control group than to the DH group. In this study, we further provide a database of gene expression changes induced by surgical creation of DH and consecutive TO in the rabbit model. Future treatment strategies could be developed using this dataset. We also discuss the most relevant genes that are involved in CDH.

Original language	English
Pages (from-to)	221-228
Number of pages	8
Journal	Disease Models & Mechanisms
Volume	9
Issue number	2
DOIs	https://doi.org/10.1242/dmm.021626
Publication status	Published - 1 Feb 2016
Externally published	Yes

Bibliographical note

Funding:
J.D. receives a fundamental clinical research grant of the Fonds Wetenschappelijk
Onderzoek Vlaanderen (FWO; 18.01207). A.C.E. is supported by the Erasmus+
Program of the European Union (Framework agreement number 2013-0040;
contract 1011990). This publication reflects the views only of the authors, and the
European Commission cannot be held responsible for any use that may be made of
the information contained therein.

© 2016. Published by The Company of Biologists Ltd.

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10.1242/dmm.021626

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title = "Pulmonary transcriptome analysis in the surgically induced rabbit model of diaphragmatic hernia treated with fetal tracheal occlusion",

abstract = "Congenital diaphragmatic hernia (CDH) is a malformation leading to pulmonary hypoplasia, which can be treated in utero by fetal tracheal occlusion (TO). However, the changes of gene expression induced by TO remain largely unknown but could be used to further improve the clinically used prenatal treatment of this devastating malformation. Therefore, we aimed to investigate the pulmonary transcriptome changes caused by surgical induction of diaphragmatic hernia (DH) and additional TO in the fetal rabbit model. Induction of DH was associated with 378 upregulated genes compared to controls when allowing a false-discovery rate (FDR) of 0.1 and a fold change (FC) of 2. Those genes were again downregulated by consecutive TO. But DH+TO was associated with an upregulation of 157 genes compared to DH and controls. When being compared to control lungs, 106 genes were downregulated in the DH group and were not changed by TO. Therefore, the overall pattern of gene expression in DH+TO is more similar to the control group than to the DH group. In this study, we further provide a database of gene expression changes induced by surgical creation of DH and consecutive TO in the rabbit model. Future treatment strategies could be developed using this dataset. We also discuss the most relevant genes that are involved in CDH.",

author = "Engels, {Alexander C} and Brady, {Paul D} and Molka Kammoun and {Finalet Ferreiro}, Julio and Philip DeKoninck and Masayuki Endo and Jaan Toelen and Vermeesch, {Joris R} and Jan Deprest",

note = "Funding: J.D. receives a fundamental clinical research grant of the Fonds Wetenschappelijk Onderzoek Vlaanderen (FWO; 18.01207). A.C.E. is supported by the Erasmus+ Program of the European Union (Framework agreement number 2013-0040; contract 1011990). This publication reflects the views only of the authors, and the European Commission cannot be held responsible for any use that may be made of the information contained therein. {\textcopyright} 2016. Published by The Company of Biologists Ltd.",

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AU - DeKoninck, Philip

AU - Endo, Masayuki

AU - Toelen, Jaan

AU - Vermeesch, Joris R

AU - Deprest, Jan

N1 - Funding: J.D. receives a fundamental clinical research grant of the Fonds Wetenschappelijk Onderzoek Vlaanderen (FWO; 18.01207). A.C.E. is supported by the Erasmus+ Program of the European Union (Framework agreement number 2013-0040; contract 1011990). This publication reflects the views only of the authors, and the European Commission cannot be held responsible for any use that may be made of the information contained therein. © 2016. Published by The Company of Biologists Ltd.

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N2 - Congenital diaphragmatic hernia (CDH) is a malformation leading to pulmonary hypoplasia, which can be treated in utero by fetal tracheal occlusion (TO). However, the changes of gene expression induced by TO remain largely unknown but could be used to further improve the clinically used prenatal treatment of this devastating malformation. Therefore, we aimed to investigate the pulmonary transcriptome changes caused by surgical induction of diaphragmatic hernia (DH) and additional TO in the fetal rabbit model. Induction of DH was associated with 378 upregulated genes compared to controls when allowing a false-discovery rate (FDR) of 0.1 and a fold change (FC) of 2. Those genes were again downregulated by consecutive TO. But DH+TO was associated with an upregulation of 157 genes compared to DH and controls. When being compared to control lungs, 106 genes were downregulated in the DH group and were not changed by TO. Therefore, the overall pattern of gene expression in DH+TO is more similar to the control group than to the DH group. In this study, we further provide a database of gene expression changes induced by surgical creation of DH and consecutive TO in the rabbit model. Future treatment strategies could be developed using this dataset. We also discuss the most relevant genes that are involved in CDH.

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Pulmonary transcriptome analysis in the surgically induced rabbit model of diaphragmatic hernia treated with fetal tracheal occlusion

Abstract

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