Early-Gestation Fetal Scarless Wounds Have Less Lysyl Oxidase Expression

Background: Lysyl oxidase cross-links collagen and elastin. Because cross-linking likely influences collagen architecture, the authors compared lysyl oxidase expression during scarless and scarring fetal dermal wound repair. Methods: Excisional dermal wounds were made on E17 (gestational day 16.5) and E19 (gestational day 18.5) mouse fetuses. Skin and wound RNA was collected at 8, 12, and 24 hours. Quantitative real-time polymerase chain reaction was performed for lysyl oxidase. The effect of transforming growth factor (TGF)-&bgr;1 on lysyl oxidase expression in fetal fibroblasts was tested. Confluent primary fetal and postnatal fibroblast cultures were stimulated with TGF-&bgr;1 for 24 hours, and lysyl oxidase expression was quantitated by performing real-time polymerase chain reaction. Lysyl oxidase expression was also quantitated in unwounded fetal skin to determine its expression profile during development. Results: E17 and E19 fetal skin had approximately 2-fold greater lysyl oxidase expression than postnatal skin (p < 0.01), and fetal fibroblasts had greater baseline lysyl oxidase expression than postnatal fibroblasts. After TGF-&bgr;1 stimulation, fetal and postnatal fibroblasts responded with increases in lysyl oxidase expression. In E17 early-gestation scarless fetal wounds, lysyl oxidase had small increases (<1.5-fold) in expression from 1 to 12 hours. In late-gestation E19 scarring fetal wounds, lysyl oxidase increased 1.8-fold at 8 hours and 2-fold at 12 hours, which was significantly greater than the changes observed in E17 scarless wounds (p < 0.01 for each). Conclusions: Lysyl oxidase has greater expression in E19 late-gestation wounds that heal with scar compared with E17 early-gestation scarless wounds. This suggests a role for lysyl oxidase in scar formation.