| First Author | Zheng Z | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 6 | Pages | e90817 |
| PubMed ID | 24603701 | Mgi Jnum | J:217246 |
| Mgi Id | MGI:5613439 | Doi | 10.1371/journal.pone.0090817 |
| Citation | Zheng Z, et al. (2014) Fibromodulin-deficiency alters temporospatial expression patterns of transforming growth factor-beta ligands and receptors during adult mouse skin wound healing. PLoS One 9(6):e90817 |
| abstractText | Fibromodulin (FMOD) is a small leucine-rich proteoglycan required for scarless fetal cutaneous wound repair. Interestingly, increased FMOD levels have been correlated with decreased transforming growth factor (TGF)-beta1 expression in multiple fetal and adult rodent models. Our previous studies demonstrated that FMOD-deficiency in adult animals results in delayed wound closure and increased scar size accompanied by loose package collagen fiber networks with increased fibril diameter. In addition, we found that FMOD modulates in vitro expression and activities of TGF-beta ligands in an isoform-specific manner. In this study, temporospatial expression profiles of TGF-beta ligands and receptors in FMOD-null and wild-type (WT) mice were compared by immunohistochemical staining and quantitative reverse transcriptase-polymerase chain reaction using a full-thickness, primary intention wound closure model. During the inflammatory stage, elevated inflammatory infiltration accompanied by increased type I TGF-beta receptor levels in individual inflammatory cells was observed in FMOD-null wounds. This increased inflammation was correlated with accelerated epithelial migration during the proliferative stage. On the other hand, significantly more robust expression of TGF-beta3 and TGF-beta receptors in FMOD-null wounds during the proliferative stage was associated with delayed dermal cell migration and proliferation, which led to postponed granulation tissue formation and wound closure and increased scar size. Compared with WT controls, expression of TGF-beta ligands and receptors by FMOD-null dermal cells was markedly reduced during the remodeling stage, which may have contributed to the declined collagen synthesis capability and unordinary collagen architecture. Taken together, this study demonstrates that a single missing gene, FMOD, leads to conspicuous alternations in TGF-beta ligand and receptor expression at all stages of wound repair in various cell types. Therefore, FMOD critically coordinates temporospatial distribution of TGF-beta ligands and receptors in vivo, suggesting that FMOD modulates TGF-beta bioactivity in a complex way beyond simple physical binding to promote proper wound healing. |
