Novel differences in the expression of inflammation-associated genes between mid- and late-gestational dermal fibroblasts

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Abstract

While cutaneous wounds of late-gestational fetuses and on through adulthood result in scar formation, wounds incurred early in gestation have been shown to heal scarlessly. Unique properties of fetal fibroblasts are believed to mediate this scarless healing process. In this study, microarray analysis was used to identify differences in the gene expression profiles of cultured fibroblasts from embryonic day 15 (E15; midgestation) and embryonic day 18 (E18; late-gestation) skin. Sixty-two genes were differentially expressed and 12 of those genes are associated with inflammation, a process that correlates with scar formation in fetal wounds. One of the differentially expressed inflammatory genes was cyclooxygenase-1 (COX-1). COX-1 was more highly expressed in E18 fibroblasts than in E15 fibroblasts, and these differences were confirmed at the gene and protein level. Differences in COX-1 protein expression were also observed in fetal skin by immunohistochemical and immunofluorescence staining. The baseline differences in gene expression found in mid- and late-gestational fetal fibroblasts suggest that developmental alterations in fibroblasts could be involved in the transition from scarless to fibrotic fetal wound healing. Furthermore, baseline differences in the expression of inflammatory genes by fibroblasts in E15 and E18 skin may contribute to inflammation and scar formation late in gestation.

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