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Expression profiling of intestinal ischemia/reperfusion: first human in vivo findings
Author(s) -
Lenaerts Kaatje,
Grootjans Joep,
Derikx Joep PM,
Dam Ronald M,
Dejong Cornelis HC,
Buurman Wim A
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.565.19
Subject(s) - gene expression , gene , in vivo , gene expression profiling , biology , intestinal ischemia , jejunum , regulation of gene expression , downregulation and upregulation , microbiology and biotechnology , kegg , ischemia , reperfusion injury , medicine , genetics , gene ontology , biochemistry
To better understand the molecular mechanisms associated with intestinal ischemia/reperfusion (IR) in man, gene expression profiles were studied in a unique in vivo human experimental model. In this model, an isolated part of jejunum, to be removed during a standard surgical procedure, was subjected to 30 or 45 minutes of ischemia, followed by 30 and 120 minutes of reperfusion. Jejunal tissue exposed to IR as well as control tissue was collected. Total RNA was prepared and whole‐genome expression was assessed using Illumina HT‐12 expression beadchips containing 48,803 probes. GeneSpring X10 was used to identify differences in gene expression. Expression of 661 genes was significantly changed (p<0.05) during intestinal IR with a fold change of at least 1.5. The most highly upregulated genes code for heat shock proteins and members of the Fos and Jun families. Accordingly, overrepresented gene ontology categories (p<0.05) in the list of genes include stress response and regulation of cell proliferation. Furthermore, mapping changed genes within a pathway database showed that the EGFR1, TGFBR and TNFalpha/NF‐kB pathways are significantly affected in response to IR. This is the first study that examines global gene expression changes in the human intestine in response to IR. Identification of these transcriptional changes provides new targets to reduce intestinal IR‐associated morbidity and mortality.