RGD Reference Report - Analysis of Gene Expression in Experimental Pressure Ulcers in the Rat with Special Reference to Inflammatory Cytokines. - Rat Genome Database

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Analysis of Gene Expression in Experimental Pressure Ulcers in the Rat with Special Reference to Inflammatory Cytokines.

Authors: Kurose, T  Hashimoto, M  Ozawa, J  Kawamata, S 
Citation: Kurose T, etal., PLoS One. 2015 Jul 15;10(7):e0132622. doi: 10.1371/journal.pone.0132622. eCollection 2015.
RGD ID: 11049489
Pubmed: PMID:26177082   (View Abstract at PubMed)
PMCID: PMC4503587   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0132622   (Journal Full-text)

Pressure ulcers have been investigated in a few animal models, but the molecular mechanisms of pressure ulcers are not well understood. We hypothesized that pressure results in up-regulation of inflammatory cytokines and those cytokines contribute to the formation of pressure ulcers. We measured genome-wide changes in transcript levels after compression, and focused especially on inflammatory cytokines. The abdominal wall of rats was compressed at 100 mmHg for 4 hours by two magnets. Specimens were obtained 12 hours, 1, or 3 days after compression, and analyzed by light microscopy, microarray, Real-Time PCR, and ELISA. The skin and subcutaneous tissue in the compressed area were markedly thickened. The microarray showed that numerous genes were up-regulated after the compression. Up-regulated genes were involved in apoptosis, inflammation, oxidative stress, proteolysis, hypoxia, and so on. Real-Time PCR showed the up-regulation of granulocyte-macrophage colony stimulating factor (GM-CSF), interferon gamma (IFN-gamma), interleukin 1beta (IL-1beta), interleukin 1 receptor antagonist gene (IL1Ra), interleukin 6 (IL-6), interleukin 10 (IL-10), matrix metalloproteinase 3 (MMP-3), tissue inhibitor of metalloproteinase 1 (TIMP-1), and tumor necrosis factor alpha (TNF-alpha) at 12 hours, IFN-gamma, IL-6, IL-10, MMP-3, and TIMP-1 at 1 day, and IFN-gamma, IL-6, and MMP-3 at 3 days. Some genes from subcutaneous tissue were up-regulated temporarily, and others were kept at high levels of expression. ELISA data showed that the concentrations of IL-1beta and IL-6 proteins were most notably increased following compression. Prolonged up-regulation of IL-1beta, and IL-6 might enhance local inflammation, and continuous local inflammation may contribute to the pressure ulcer formation. In addition, GM-CSF, IFN-gamma, MMP-3, and TIMP-1 were not reported previously in the wound healing process, and those genes may have a role in development of the pressure ulcers. Expression data from Real-Time PCR were generally in good agreement with those of the microarray. Our microarray data were useful for identifying genes involved in pressure ulcer formation. However, the expression levels of the genes didn't necessarily correspond with protein production. As such, the functions of these cytokines need to be further investigated.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
decubitus ulcer  ISOIl10 (Rattus norvegicus)11049489; 11049489mRNA:increased expression:skinRGD 
decubitus ulcer  IEP 11049489mRNA:increased expression:skinRGD 

Objects Annotated

Genes (Rattus norvegicus)
Il10  (interleukin 10)

Genes (Mus musculus)
Il10  (interleukin 10)

Genes (Homo sapiens)
IL10  (interleukin 10)


Additional Information