Zheng, ZhongNguyen, CalvinZhang, XinliKhorasani, HoomanWang, Joyce ZZara, Janette NChu, FranklinYin, WeiPang, ShenLe, AnhTing, KangSoo, Chia2023-05-222023-05-222011-03-012022-06-16https://repository.upenn.edu/handle/20.500.14332/9245Fibromodulin (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.EMTREE drug terms: collagenfibromodulintransforming growth factor beta receptor 1transforming growth factor beta receptor 2transforming growth factor beta3 EMTREE medical terms: animal cellanimal experimentanimal modelanimal tissuearticlecell migrationcontrolled studyhistopathologymalemigration inhibitionmorphometricsmousenonhumanpriority journalscar formationsignal transductionskin fibroblastskin injurywound closurewound healingDentistryEndodontics and EndodontologyOral and Maxillofacial SurgeryOral Biology and Oral PathologyPeriodontics and PeriodontologyArticle