Fibromodulin Is Essential for Fetal-Type Scarless Cutaneous Wound Healing.
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.
Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California; UCLA Division of Plastic and Reconstructive Surgery, the Department of Orthopaedic Surgery, and the Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, California.
Zhong
Z
Zheng
Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California.
Xinli
X
Zhang
Saul & Joyce Brandman Breast Center, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.
Catherine
C
Dang
Hoag Hospital, Newport Beach, California.
Steven
S
Beanes
Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Grace X
GX
Chang
Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California.
Yao
Y
Chen
Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California.
Chen-Shuang
CS
Li
Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California.
Kevin S
KS
Lee
Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California; UCLA Division of Plastic and Reconstructive Surgery, the Department of Orthopaedic Surgery, and the Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, California; Department of Bioengineering, School of Engineering, University of California, Los Angeles, Los Angeles, California. Electronic address: kting@dentistry.ucla.edu.
Kang
K
Ting
UCLA Division of Plastic and Reconstructive Surgery, the Department of Orthopaedic Surgery, and the Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, California. Electronic address: bsoo@ucla.edu.
Chia
C
Soo
D000818:Animals; D002921:Cicatrix / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D005260:Female; D005333:Fetus; D000071235:Fibromodulin / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005865:Gestational Age; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000196:embryology / Q000293:injuries* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing
D053773:Transforming Growth Factor beta1; D000071235:Fibromodulin; D003094:Collagen
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