Departmental Papers (Dental)
Title
Delayed Wound Closure in Fibromodulin-Deficient Mice Is Associated with Increased TGF-β3 Signaling
Document Type
Journal Article
Date of this Version
3-2011
Publication Source
Journal of Investigative Dermatology
Volume
131
Issue
3
Start Page
769
Last Page
778
DOI
10.1038/jid.2010.381
Abstract
Fibromodulin (FMOD), a small leucine-rich proteoglycan, mediates scarless fetal skin wound repair through, in part, transforming growth factor-Β (TGF-Β) modulation. Using an adult fmod-null (fmod -/-) mouse model, this study further elucidates the interplay between FMOD and TGF-Β expression during cutaneous repair and scar formation. Full-thickness skin wounds on fmod -/- and wild-type (WT) mice were closed primarily and analyzed. Histomorphometry revealed delayed dermal cell migration leading to delayed wound closure and significantly increased scar size in fmod -/- mice relative to WT, which was partially rescued by exogenous FMOD administration. In addition, fmod -/- wounds exhibited early elevation (within 24 hours post-wounding) of type I and type II TGF-Β receptors as well as unexpectedly high fibroblast expression of TGF-Β3, a molecule with reported antifibrotic and antimigratory effects. Consistent with elevated fibroblastic TGF-Β3, fmod -/- fibroblasts were significantly less motile than WT fibroblasts. fmod -/- fibroblasts were also more susceptible to migration inhibition by TGF-Β3, leading to profound delays in dermal cell migration. Increased scarring in fmod -/- mice indicates that TGF-Β3's antimotility effects predominate over its antifibrotic effects when high TGF-Β3 levels disrupt early fibroblastic wound ingress. These studies demonstrate that FMOD presence is critical for proper temporospatial coordination of wound healing events and normal TGF-Β bioactivity. © 2011 The Society for Investigative Dermatology.
Keywords
EMTREE drug terms: collagen, fibromodulin, transforming growth factor beta receptor 1, transforming growth factor beta receptor 2, transforming growth factor beta3 EMTREE medical terms: animal cell, animal experiment, animal model, animal tissue, article, cell migration, controlled study, histopathology, male, migration inhibition, morphometrics, mouse, nonhuman, priority journal, scar formation, signal transduction, skin fibroblast, skin injury, wound closure, wound healing
Recommended Citation
Zheng, Z., Nguyen, C., Zhang, X., Khorasani, H., Wang, J. Z., Zara, J. N., Chu, F., Yin, W., Pang, S., Le, A., Ting, K., & Soo, C. (2011). Delayed Wound Closure in Fibromodulin-Deficient Mice Is Associated with Increased TGF-β3 Signaling. Journal of Investigative Dermatology, 131 (3), 769-778. http://dx.doi.org/10.1038/jid.2010.381
Included in
Endodontics and Endodontology Commons, Oral and Maxillofacial Surgery Commons, Oral Biology and Oral Pathology Commons, Periodontics and Periodontology Commons
Date Posted: 10 February 2023
This document has been peer reviewed.
Comments
At the time of publication, author Anh Le was affiliated with the University of Southern California. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.