Location: Children's Nutrition Research CenterTitle: Fetal wound healing using a genetically modified murine model: the contribution of P-selectin Author
|Smith, C. Wayne|
Submitted to: Journal of Pediatric Surgery
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/7/2007
Publication Date: 4/4/2008
Citation: Naik-Mathuria, B., Gay, A.N., Yu, L., Hsu, J.E., Smith, C., Olutoye, O.0. 2008. Fetal wound healing using a genetically modified murine model: The contribution of P-selectin. Journal of Pediatric Surgery. 43(4):675-82. Interpretive Summary: This research deals with the mechanisms of wound healing, a process that is delayed in patients with obesity and/or diabetes. We studied fetal wound healing looking for reasons why fetal wounds heal so well, and possible approaches to applying this information to improving wounds in adults. In a mouse model of skin wounds, and we found for the first time the importance of blood protein called P-selectin. Future studies will investigate this protein and its functions in obesity and diabetes in a mouse model.
Technical Abstract: During early gestation, fetal wounds heal with paucity of inflammation and absent scar formation. P-selectin is an adhesion molecule that is important for leukocyte recruitment to injury sites. We used a murine fetal wound healing model to study the specific contribution of P-selectin to scarless wound repair. Linear excisional wounds were created on the dorsa of E15.5 and E17.5 gestation fetuses in wild-type and P-selectin (-/-) mice (term = 19 days). Wounds were harvested at various time-points after wounding and analyzed using histology and immunohistochemistry. The E15.5 wounds in both wild-type and P-selectin (-/-) fetuses healed scarlessly and with minimal inflammation, whereas E17.5 wounds healed with fibrosis and inflammation. However, the scars of the P-selectin (-/-) wounds appeared slightly different than wild-type. There were significantly more inflammatory cells in E17.5 wild-type wounds 6 hours after injury (P < .001), but the difference was no longer significant by 24 hours. Finally, reepithelialization was slower in the E15.5 knockout wounds compared to their wild-type counterparts. Absence of P-selectin delays inflammatory cell recruitment and reepithelialization of fetal wounds; however, scar formation still occurs in late gestation wounds. The contribution of specific molecules to fetal wound healing can be elucidated using murine knockout or transgenic models.