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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-4-27
pubmed:abstractText
This study focused on the regulation of prostaglandin (PG) production in diabetes-impaired wound tissue. Cyclooxygenase (COX)-1 and -2 expression and activity were severely dysregulated in chronic wounds of diabetic ob/ob mice. Those wounds were characterized by a reduced expression of COX-1 and the presence of strongly elevated levels of COX-2 when compared with conditions observed in healthy animals. Resolution of the diabetic and impaired wound-healing phenotype by systemic administration of leptin into ob/ob mice increased COX-1 expression in wound margin keratinocytes and decreased COX-2 expression in inner wound areas to levels found in wild-type animals. Notably, improved wound healing was characterized by a marked increase in PGE2/PGD2 biosynthesis that colocalized with induced COX-1 in new tissue at the margin of the wound. COX-2 expression did not significantly contribute to PGE2/PGD2 production in impaired wound tissue. Accordingly, only late wound tissue from SC-560-treated (selective COX-1 inhibitor) but not celecoxib-treated (selective COX-2 inhibitor) ob/ob mice exhibited a severe loss in PGE2, PGD2, and prostacyclin at the wound site, and this change was associated with reduced keratinocyte numbers in the neo-epithelia. These data constitute strong evidence that a dysregulation of COX-1-coupled prostaglandin contributes to diabetes-impaired wound healing.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1543-51
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15855344-Animals, pubmed-meshheading:15855344-Cyclooxygenase 1, pubmed-meshheading:15855344-Cyclooxygenase 2, pubmed-meshheading:15855344-Diabetes Mellitus, Type 2, pubmed-meshheading:15855344-Dinoprostone, pubmed-meshheading:15855344-Disease Models, Animal, pubmed-meshheading:15855344-Inflammation, pubmed-meshheading:15855344-Leptin, pubmed-meshheading:15855344-Membrane Proteins, pubmed-meshheading:15855344-Mice, pubmed-meshheading:15855344-Mice, Inbred C57BL, pubmed-meshheading:15855344-Mice, Obese, pubmed-meshheading:15855344-Obesity, pubmed-meshheading:15855344-Prostaglandin D2, pubmed-meshheading:15855344-Prostaglandin-Endoperoxide Synthases, pubmed-meshheading:15855344-Recombinant Proteins, pubmed-meshheading:15855344-Wound Healing, pubmed-meshheading:15855344-Wounds and Injuries
pubmed:year
2005
pubmed:articleTitle
Wound inflammation in diabetic ob/ob mice: functional coupling of prostaglandin biosynthesis to cyclooxygenase-1 activity in diabetes-impaired wound healing.
pubmed:affiliation
Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der JW Goethe-Universität Frankfurt/M., Theodor-Stern-Kai 7, D-60590 Frankfurt/M., Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't