Departmental Papers (Dental)

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.

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.

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

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Date Posted: 10 February 2023

This document has been peer reviewed.