Document Type
Journal Article
Publication Date
1-1-2015
Journal
Critical Care
Volume
19
Issue
1
Inclusive Pages
327
DOI
10.1186/s13054-015-1052-0
Abstract
INTRODUCTION: Experimental data from animal models of sepsis support a role for a transcription factor, nuclear erythroid-related factor 2 p45-related factor 2 (Nrf2), as a master regulator of antioxidant and detoxifying genes and intermediary metabolism during stress. Prior analysis of a pediatric septic shock transcriptomic database showed that the Nrf2 response is a top 5 upregulated signaling pathway in early pediatric septic shock.
METHODS: We conducted a focused analysis of 267 Nrf2-linked genes using a multicenter, genome-wide expression database of 180 children with septic shock 10 years of age or younger and 53 healthy controls. The analysis involved RNA isolated from whole blood within 24 h of pediatric intensive care unit admission for septic shock and a false discovery rate of 5 %. We compared differentially expressed genes from (1) patients with septic shock and healthy controls and (2) across validated gene expression-based subclasses of pediatric septic shock (endotypes A and B) using several bioinformatic methods.
RESULTS: We found upregulation of 123 Nrf2-linked genes in children with septic shock. The top gene network represented by these genes contained primarily enzymes with oxidoreductase activity involved in cellular lipid metabolism that were highly connected to the peroxisome proliferator activated receptor and the retinoic acid receptor families. Endotype A, which had higher organ failure burden and mortality, exhibited a greater downregulation of Nrf2-linked genes than endotype B, with 92 genes differentially regulated between endotypes.
CONCLUSIONS: Our findings indicate that Nrf2-linked genes may contribute to alterations in oxidative signaling and intermediary metabolism in pediatric septic shock.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Grunwell, J. R., Weiss, S. L., Cvijanovich, N. Z., Allen, G. L., Thomas, N. J., Freishtat, R. J., … Wong, H. R. (2015). Differential expression of the Nrf2-linked genes in pediatric septic shock. Critical Care, 19(1), 327. http://doi.org/10.1186/s13054-015-1052-0
Peer Reviewed
1
Open Access
1
Comments
Reproduced with permission of BioMed Central Ltd. Critical Care.