| First Author | Zheng Z | Year | 2011 |
| Journal | J Invest Dermatol | Volume | 131 |
| Issue | 3 | Pages | 769-78 |
| PubMed ID | 21191417 | Mgi Jnum | J:180838 |
| Mgi Id | MGI:5307963 | Doi | 10.1038/jid.2010.381 |
| Citation | Zheng Z, et al. (2011) Delayed wound closure in fibromodulin-deficient mice is associated with increased TGF-beta3 signaling. J Invest Dermatol 131(3):769-78 |
| abstractText | Fibromodulin (FMOD), a small leucine-rich proteoglycan, mediates scarless fetal skin wound repair through, in part, transforming growth factor-beta (TGF-beta) modulation. Using an adult fmod-null (fmod(-/-)) mouse model, this study further elucidates the interplay between FMOD and TGF-beta 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-beta receptors as well as unexpectedly high fibroblast expression of TGF-beta3, a molecule with reported antifibrotic and antimigratory effects. Consistent with elevated fibroblastic TGF-beta3, fmod(-/-) fibroblasts were significantly less motile than WT fibroblasts. fmod(-/-) fibroblasts were also more susceptible to migration inhibition by TGF-beta3, leading to profound delays in dermal cell migration. Increased scarring in fmod(-/-) mice indicates that TGF-beta3's antimotility effects predominate over its antifibrotic effects when high TGF-beta3 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-beta bioactivity. |
