| First Author | Kämpfer H | Year | 2005 |
| Journal | Diabetes | Volume | 54 |
| Issue | 5 | Pages | 1543-51 |
| PubMed ID | 15855344 | Mgi Jnum | J:105193 |
| Mgi Id | MGI:3614306 | Doi | 10.2337/diabetes.54.5.1543 |
| Citation | Kampfer H, et al. (2005) Wound inflammation in diabetic ob/ob mice: functional coupling of prostaglandin biosynthesis to cyclooxygenase-1 activity in diabetes-impaired wound healing. Diabetes 54(5):1543-51 |
| 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. |
