Emdogain-Regulated Gene Expression in Palatal Fibroblasts Requires TGF-βRI Kinase Signaling

Genome-wide microarrays have suggested that Emdogain regulates TGF-beta target genes in gingival and palatal fibroblasts. However, definitive support for this contention and the extent to which TGF-beta signaling contributes to the effects of Emdogain has remained elusive. We therefore studied the role of the TGF-beta receptor I (TGF-beta RI) kinase to mediate the effect of Emdogain on palatal fibroblasts. Palatal fibroblasts were exposed to Emdogain with and without the inhibitor for TGF-beta RI kinase, SB431542. Emdogain caused 39 coding genes to be differentially expressed in palatal fibroblasts by microarray analysis (p<0.05; >10-fold). Importantly, in the presence of the TGF-beta RI kinase inhibitor SB431542, Emdogain failed to cause any significant changes in gene expression. Consistent with this mechanism, three independent TGF-beta RI kinase inhibitors and a TGF-beta neutralizing antibody abrogated the increased expression of IL-11, a selected Emdogain target gene. The MAPK inhibitors SB203580 and U0126 lowered the impact of Emdogain on IL-11 expression. The data support that TGF-beta RI kinase activity is necessary to mediate the effects of Emdogain on gene expression in vitro.