Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome

Wong, Hector R.; Shanley, Thomas P.; Sakthivel, Bhuvaneswari; Cvijanovich, Natalie Z.; Lin, Richard J.; Allen, Geoffrey L.; Thomas, Neal J.; Doctor, Allan; Kalyanaraman, Meena; Tofil, Nancy M.; Penfil, Scott; Monaco, Marie; Tagavilla, Mary Ann; Odoms, Kelli; Dunsmore, Katherine E.; Barnes, Michael; Aronow, Bruce J.

doi:10.1152/physiolgenomics.00024.2007

Cited by 219 publications

(300 citation statements)

References 43 publications

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“…Six of the 35 focus genes (17 percent) are different between the day one and the day three BCL2-related networks. 6 This network contains multiple HLA genes (HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DQA1, HLA-DQB1, HLA-DRA, and HLA-DRB1).…”

Section: 34mentioning

confidence: 99%

“…We have suggested that one powerful approach to more comprehensively understand the inherent biological complexity of pediatric septic shock involves translational research at the genomic level (5,6). The feasibility of a genomic approach to increase our understanding of septic shock pathobiology is indicated by a series of recent studies (7)(8)(9)(10)(11)(12), including our own initial report (6). Furthermore, a comprehensive, unbiased examination of gene transcripts at the level of the whole genome may identify novel biological mechanisms and therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

“…In a previous study, we generated an unprecedented, genome-level expression profile dataset of pediatric septic shock specifically focused on a single time point, within the first 24 h of presentation to the PICU (6). The previous dataset demonstrated the feasibility of conducting genome-centered, translational research in critically ill children.…”

Section: Introductionmentioning

confidence: 99%

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Genome-Level Longitudinal Expression of Signaling Pathways and Gene Networks in Pediatric Septic Shock

Shanley

Cvijanovich²,

Lin

et al. 2007

Mol Med

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116

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We have conducted longitudinal studies focused on the expression profiles of signaling pathways and gene networks in children with septic shock. Genome-level expression profiles were generated from whole blood-derived RNA of children with septic shock (n = 30) corresponding to day one and day three of septic shock, respectively. Based on sequential statistical and expression filters, day one and day three of septic shock were characterized by differential regulation of 2,142 and 2,504 gene probes, respectively, relative to controls (n = 15). Venn analysis demonstrated 239 unique genes in the day one dataset, 598 unique genes in the day three dataset, and 1,906 genes common to both datasets. Functional analyses demonstrated timedependent, differential regulation of genes involved in multiple signaling pathways and gene networks primarily related to immunity and inflammation. Notably, multiple and distinct gene networks involving T cell-and MHC antigen-related biology were persistently downregulated on both day one and day three. Further analyses demonstrated large scale, persistent downregulation of genes corresponding to functional annotations related to zinc homeostasis. These data represent the largest reported cohort of patients with septic shock subjected to longitudinal genome-level expression profiling. The data further advance our genome-level understanding of pediatric septic shock and support novel hypotheses.

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Section: 34mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genome-Level Longitudinal Expression of Signaling Pathways and Gene Networks in Pediatric Septic Shock

Shanley

Cvijanovich²,

Lin

et al. 2007

Mol Med

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116

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“…Por otra parte, ha sido demostrado en un modelo experimental animal y en pacientes sépticos que la presencia de menores niveles séricos de zinc se asocia a mayor mortalidad 45 .…”

Section: Patología Infecciosaunclassified

“…Estudios de asociación del genoma completo (GWAS, del inglés Genome-Wide Association Study) han comunicado que el shock séptico en el niño se caracteriza por una precoz, persistente y concomitante represión de programas genéticos relacionados con el sistema inmune adaptativo y la biología del zinc 43,45 , identificándose posteriormente que una subclase de esta población presentó un fenotipo clínico asociado a un peor pronóstico vital. Dado la deficiencia que presenta en la inmunidad adaptativa el paciente con SD, la cual se exacerba en el paciente con shock séptico, se debiera disponer a futuro mediante una subclasificación a nivel genómico, de una terapia específicamente orientada.…”

Section: Patología Infecciosaunclassified

El niño con Síndrome de Down en la Unidad de Cuidados Intensivos

F¹,

F²,

B³

et al. 2017

Rev. chil. pediatr.

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Zinc signals and immune function

2013

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For more than 50 years, it has been known that zinc deficiency compromises immune function. During this time, knowledge about the biochemistry of zinc has continued to grow, but only recent years have provided in-depth molecular insights into the multiple aspects of zinc as a regulator of immunity. A network based on ZnT and ZIP proteins for transport and metallothionein for storage tightly regulates zinc availability, and virtually all aspects of innate and adaptive immunity are affected by zinc. In vivo, zinc deficiency alters the number and function of neutrophil granulocytes, monocytes, natural killer (NK)-, T-, and B-cells. T cell functions and balance between the different subsets are particularly susceptible to changes in zinc status. This article focuses in particular on the main mechanisms by which zinc ions exert essential functions in the immune system. On the one hand, this includes tightly protein bound zinc ions serving catalytic or structural functions in a multitude of different proteins, in particular enzymes and transcription factors. On the other hand, increasing evidence arises for a regulatory role of free zinc ions in signal transduction, especially in cells of the immune system. Identification of several molecular targets, including phosphatases, phosphodiesterases, caspases, and kinases suggest that zinc ions are a second messenger regulating signal transduction in various kinds of immune cells.

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Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome

Abstract: Barnes M, Aronow BJ. Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome.

Cited by 219 publications

References 43 publications

Genome-Level Longitudinal Expression of Signaling Pathways and Gene Networks in Pediatric Septic Shock

Genome-Level Longitudinal Expression of Signaling Pathways and Gene Networks in Pediatric Septic Shock

El niño con Síndrome de Down en la Unidad de Cuidados Intensivos

Zinc signals and immune function

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