Umbilical cord gene expression reveals the molecular architecture of the fetal inflammatory response in extremely preterm newborns

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• dc.contributor.author Costa, Danielca
• dc.contributor.author Castelo Valdueza, Robertca
• dc.date.accessioned 2016-04-08T16:16:17Z
• dc.date.available 2016-04-08T16:16:17Z
• dc.date.issued 2016
• dc.description.abstract BACKGROUND: The fetal inflammatory response (FIR) in placental membranes to an intrauterine infection often precedes premature birth raising neonatal mortality and morbidity. However, the precise molecular events behind FIR still remain largely unknown, and little has been investigated at gene expression level. METHODS: We collected publicly available microarray expression data profiling umbilical cord (UC) tissue derived from the cohort of extremely low gestational age newborns (ELGANs) and interrogate them for differentially expressed (DE) genes between FIR and non-FIR-affected ELGANs. RESULTS: We found a broad and complex FIR UC gene expression signature, changing up to 19% (3,896/20,155) of all human genes at 1% false discovery rate. Significant changes of a minimum 50% magnitude (1,097/3,896) affect the upregulation of many inflammatory pathways and molecules, such as cytokines, toll-like receptors, and calgranulins. Remarkably, they also include the downregulation of neurodevelopmental pathways and genes, such as Fragile-X mental retardation 1 (FMR1), contactin 1 (CNTN1), and adenomatous polyposis coli (APC). CONCLUSION: The FIR expression signature in UC tissue contains molecular clues about signaling pathways that trigger FIR, and it is consistent with an acute inflammatory response by fetal innate and adaptive immune systems, which participate in the pathogenesis of neonatal brain damage.ca
• dc.description.sponsorship This study was supported by a grant from the Spanish Ministry of Economy and Competitiveness (TIN2011-22826).
• dc.format.mimetype application/pdfca
• dc.identifier.citation Costa D, Castelo R. Umbilical cord gene expression reveals the molecular architecture of the fetal inflammatory response in extremely preterm newborns. Pediatric research. 2016;79(3):473-81. DOI: 10.1038/pr.2015.233ca
• dc.identifier.doi http://dx.doi.org/10.1038/pr.2015.233
• dc.identifier.issn 0031-3998
• dc.identifier.uri http://hdl.handle.net/10230/26064
• dc.language.iso engca
• dc.publisher Nature Publishing Groupca
• dc.relation.ispartof Pediatric research. 2016;79(3):473-81
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/TIN2011-22826
• dc.rights This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the materialca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/4.0/ca
• dc.subject.other Gens -- Anàlisi -- Informàticaca
• dc.subject.other Infants nadons -- Malaltiesca
• dc.title Umbilical cord gene expression reveals the molecular architecture of the fetal inflammatory response in extremely preterm newbornsca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca