Altered gene expression in acute systemic inflammation detected by complete coverage of the human liver transcriptome

Coulouarn, Cédric; Lefebvre, Grégory; Derambure, Céline; Lequerré, Thierry; Scotté, Michel; Audigier, François; Cellier, Dominique; Daveau, Maryvonne; Salier, Jean‐Philippe

doi:10.1002/hep.20052

Cited by 30 publications

(65 citation statements)

References 47 publications

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“…Several defensin (Defcr2, Defcr9, Defcr6, and Defb6), heat shock (Hspa5, Hspb1, and Hspa8), immune response (Gbp2 and Xbp1), and acute-phase response (Itih3) genes were upregulated in Nas1 Ϫ/Ϫ mice ( Table 2). Similar transcriptional responses were reported during acute systemic inflammation (13). However, Nas1 Ϫ/Ϫ mice showed no evidence of liver inflammation in hematoxylin-and eosin-stained sections (16), suggesting an injury in extrahepatic tissues.…”

Section: Nas1supporting

confidence: 75%

Transcriptional profile reveals altered hepatic lipid and cholesterol metabolism in hyposulfatemic NaS1 null mice

Dawson

Gardiner

Grimmond

et al. 2006

Physiological Genomics

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. Transcriptional profile reveals altered hepatic lipid and cholesterol metabolism in hyposulfatemic NaS1 null mice. Physiol Genomics 26: 116 -124, 2006. First published April 18, 2006 doi:10.1152/physiolgenomics.00300.2005.-Sulfate plays an essential role in human growth and development, and its circulating levels are maintained by the renal Na ϩ -SO 4 2Ϫ cotransporter, NaS1. We previously generated a NaS1 knockout (Nas1 Ϫ/Ϫ ) mouse, an animal model for hyposulfatemia, that exhibits reduced growth and liver abnormalities including hepatomegaly. In this study, we investigated the hepatic gene expression profile of Nas1 Ϫ/Ϫ mice using oligonucleotide microarrays. The mRNA expression levels of 92 genes with known functional roles in metabolism, cell signaling, cell defense, immune response, cell structure, transcription, or protein synthesis were increased (n ϭ 51) or decreased (n ϭ 41) in Nas1 Ϫ/Ϫ mice when compared with Nas1 ϩ/ϩ mice. The most upregulated transcript levels in Nas1 Ϫ/Ϫ mice were found for the sulfotransferase genes, Sult3a1 (Ϸ500% increase) and Sult2a2 (100% increase), whereas the metallothionein-1 gene, Mt1, was among the most downregulated genes (70% decrease). Several genes involved in lipid and cholesterol metabolism, including Scd1, Acly, Gpam, Elov16, Acsl5, Mvd, Insig1, and Apoa4, were found to be upregulated (Ն30% increase) in Nas1 Ϫ/Ϫ mice. In addition, Nas1 Ϫ/Ϫ mice exhibited increased levels of hepatic lipid (Ϸ16% increase), serum cholesterol (Ϸ20% increase), and low-density lipoprotein (Ϸ100% increase) and reduced hepatic glycogen (Ϸ50% decrease) levels. In conclusion, these data suggest an altered lipid and cholesterol metabolism in the hyposulfatemic Nas1 Ϫ/Ϫ mouse and provide new insights into the metabolic state of the liver in Nas1 Ϫ/Ϫ mice.

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Section: Nas1supporting

confidence: 75%

Transcriptional profile reveals altered hepatic lipid and cholesterol metabolism in hyposulfatemic NaS1 null mice

Dawson

Gardiner

Grimmond

et al. 2006

Physiological Genomics

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“…A common repression of genes involved in immune response was also prominent in all models, possibly due to alterations in hepatic function, because expression of innate immunity-related genes is a characteristic of the normal liver. 26,27 In contrast, several functional categories appeared to be differentially regulated by E2f1 and c-Myc. Thus, in c-Myc overexpressing livers, genes involved in protein synthesis and catabolism were respectively induced and repressed, reflecting a specific role for c-Myc in the control of translational machinery.…”

Section: Resultsmentioning

confidence: 87%

Oncogene-specific gene expression signatures at preneoplastic stage in mice define distinct mechanisms of hepatocarcinogenesis

et al. 2006

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We applied a genome-wide microarray analysis to three transgenic mouse models of liver cancer in which targeted overexpression of c-Myc, E2f1, and a combination of the two was driven by the albumin promoter. Although gene expression profiles in HCC derived in all three transgenic lines were highly similar, oncogene-specific gene expression signatures were identified at an early dysplastic stage of hepatocarcinogenesis. Overexpression of E2f1 was associated with a strong alteration in lipid metabolism, and Srebp1was identified as a candidate transcription factor responsible for lipogenic enzyme induction. The molecular signature of c-Myc overexpression included the induction of more than 60 genes involved in the translational machinery that correlated with an increase in liver mass. In contrast, the combined activity of c-Myc and E2f1 specifically enhanced the expression of genes involved in mitochondrial metabolism-particularly the components of the respiratory chain-and correlated with an increased ATP synthesis. Thus, the results suggest that E2f1, c-Myc, and their combination may promote liver tumor development by distinct mechanisms. In conclusion, determination of tissue-specific oncogene expression signatures might be useful to identify conserved expression modules in human cancers. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

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“…When sequencing 174 selected clones these authors identified 23 already known AP-proteins, 31 proteins known but so far not related to the AP-response, and discovered 36 novel proteins induced in the liver during turpentine-induced inflammation. More recently the Salier's group studied changes in the human liver transcriptome in patients www.intechopen.com with systemic inflammation (Coulouarn et al, 2004). They found over 150 specific mRNAs expressed in the liver and correlating with the extent of inflammatory processes.…”

Section: Molecular Mechanisms Of Induced Synthesis Of Acute Phase Promentioning

confidence: 99%

Regulatory Mechanisms Controlling Inflammation and Synthesis of Acute Phase Proteins

Jura¹,

Koj²

2011

Acute Phase Proteins - Regulation and Functions of Acute Phase Proteins

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Altered gene expression in acute systemic inflammation detected by complete coverage of the human liver transcriptome

Cited by 30 publications

References 47 publications

Transcriptional profile reveals altered hepatic lipid and cholesterol metabolism in hyposulfatemic NaS1 null mice

Transcriptional profile reveals altered hepatic lipid and cholesterol metabolism in hyposulfatemic NaS1 null mice

Oncogene-specific gene expression signatures at preneoplastic stage in mice define distinct mechanisms of hepatocarcinogenesis

Regulatory Mechanisms Controlling Inflammation and Synthesis of Acute Phase Proteins

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