PMID- 26177082
OWN - NLM
STAT- MEDLINE
DCOM- 20160501
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 7
DP  - 2015
TI  - Analysis of Gene Expression in Experimental Pressure Ulcers in the Rat with 
      Special Reference to Inflammatory Cytokines.
PG  - e0132622
LID - 10.1371/journal.pone.0132622 [doi]
LID - e0132622
AB  - 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.
FAU - Kurose, Tomoyuki
AU  - Kurose T
AD  - Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 
      Japan.
FAU - Hashimoto, Masakazu
AU  - Hashimoto M
AD  - Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 
      Japan.
FAU - Ozawa, Junya
AU  - Ozawa J
AD  - Faculty of Health Sciences, Hiroshima International University, Hiroshima, Japan.
FAU - Kawamata, Seiichi
AU  - Kawamata S
AD  - Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150715
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cytokines)
SB  - IM
MH  - Animals
MH  - Cytokines/*genetics/metabolism
MH  - Disease Models, Animal
MH  - Gene Expression Profiling/methods
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Male
MH  - Oligonucleotide Array Sequence Analysis/methods
MH  - Pressure Ulcer/genetics/*immunology/*pathology
MH  - Rats
MH  - Up-Regulation
PMC - PMC4503587
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/07/16 06:00
MHDA- 2016/05/02 06:00
PMCR- 2015/07/15
CRDT- 2015/07/16 06:00
PHST- 2014/11/07 00:00 [received]
PHST- 2015/06/16 00:00 [accepted]
PHST- 2015/07/16 06:00 [entrez]
PHST- 2015/07/16 06:00 [pubmed]
PHST- 2016/05/02 06:00 [medline]
PHST- 2015/07/15 00:00 [pmc-release]
AID - PONE-D-14-50201 [pii]
AID - 10.1371/journal.pone.0132622 [doi]
PST - epublish
SO  - PLoS One. 2015 Jul 15;10(7):e0132622. doi: 10.1371/journal.pone.0132622. 
      eCollection 2015.