Departmental Papers (Dental)
Date of this Version
American Journal of Pathology
In contrast to adult and late-gestation fetal skin wounds, which heal with scar, early-gestation fetal skin wounds display a remarkable capacity to heal scarlessly. Although the underlying mechanism of this transition from fetal-type scarless healing to adult-type healing with scar has been actively investigated for decades, in utero restoration of scarless healing in late-gestation fetal wounds has not been reported. In this study, using loss- and gain-of-function rodent fetal wound models, we identified that fibromodulin (Fm) is essential for fetal-type scarless wound healing. In particular, we found that loss of Fm can eliminate the ability of early-gestation fetal rodents to heal without scar. Meanwhile, administration of fibromodulin protein (FM) alone was capable of restoring scarless healing in late-gestation rat fetal wounds, which naturally heal with scar, as characterized by dermal appendage restoration and organized collagen architectures that were virtually indistinguishable from those in age-matched unwounded skin. High Fm levels correlated with decreased transforming growth factor (TGF)-β1 expression and scarless repair, while low Fm levels correlated with increased TGF-β1 expression and scar formation. This study represents the first successful in utero attempt to induce scarless repair in late-gestation fetal wounds by using a single protein, Fm, and highlights the crucial role that the FM–TGF-β1 nexus plays in fetal-type scarless skin repair. © 2016 American Society for Investigative Pathology
Animals, Cicatrix, Collagen, Female, Fetus, Fibromodulin, Gene Expression Profiling, Gene Expression Regulation, Gestational Age, Male, Mice, Oligonucleotide Array Sequence Analysis, Rats, Rats, Sprague-Dawley, Skin, Transforming Growth Factor beta1, Wound Healing, collagen, collagen type 1, fibromodulin, leucine, proteoglycan, transforming growth factor beta1, collagen, fibromodulin, transforming growth factor beta1, angiogenesis, animal experiment, animal model, animal tissue, Article, clinical evaluation, controlled study, disease association, embryo development, female, fetus, gain of function mutation, gestational age, male, nonhuman, priority journal, protein expression, rat, scarless cutaneous wound healing, skin injury, wound healing, animal, DNA microarray, embryology, gene expression profiling, gene expression regulation, genetics, injuries, metabolism, mouse, pathology, scar, skin, Sprague Dawley rat
Zheng, Z., Zhang, X., Dang, C., Beanes, S., Chang, G. X., Chen, Y., Li, C., Lee, K. S., Ting, K., & Soo, C. (2016). Fibromodulin Is Essential for Fetal-Type Scarless Cutaneous Wound Healing. American Journal of Pathology, 186 (11), 2824-2832. http://dx.doi.org/10.1016/j.ajpath.2016.07.023
Dental Materials Commons, Oral and Maxillofacial Surgery Commons, Orthodontics and Orthodontology Commons
Date Posted: 10 February 2023
This document has been peer reviewed.
At the time of publication, author Chenshuang Li was affiliated with the School of Dentistry, University of California. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.