Differential Expression of Fibromodulin, a Transforming Growth Factor-β Modulator, in Fetal Skin Development and Scarless Repair

Transforming growth factor-β (TGF-β1, -β2, and -β3) has been implicated in the ontogenetic transition from scarless fetal repair to adult repair with scar. Generally, TGF-β exerts its effects through type I and II receptors; however, TGF-β modulators such as latent TGF-β binding protein-1 (LTBP-1), decorin, biglycan, and fibromodulin can bind and potentially inhibit TGF-β activity. To more fully explore the role of TGF-β ligands, receptors, and potential modulators during skin development and wound healing, we have used a rat model that transitions from scarless fetal-type repair to adult-type repair with scar between days 16 and 18 of gestation. We showed that TGF-β ligand and receptor mRNA levels did not increase during the transition to adult-type repair in fetal skin, whereas LTBP-1 and fibromodulin expression decreased. In addition, TGF-β1 and -β3; type I, II, and III receptors; as well as LTBP-1, decorin, and biglycan were up-regulated during adult wound healing. In marked contrast, fibromodulin expression was initially down-regulated in adult repair. Immunostaining demonstrated significant fibromodulin induction 36 hours after injury in gestation day 16, but not day 19, fetal wounds. This inverse relationship between fibromodulin expression and scarring in both fetal and adult rat wound repair suggests that fibromodulin may be a biologically relevant modulator of TGF-β activity during scar formation.