title: Emdogain-regulated gene expression in palatal fibroblasts requires TGF-βRI kinase signaling.
abstract: Genome-wide microarrays have suggested that Emdogain regulates TGF-β target genes in gingival and palatal fibroblasts. However, definitive support for this contention and the extent to which TGF-β signaling contributes to the effects of Emdogain has remained elusive. We therefore studied the role of the TGF-β receptor I (TGF-βRI) kinase to mediate the effect of Emdogain on palatal fibroblasts. Palatal fibroblasts were exposed to Emdogain with and without the inhibitor for TGF-βRI 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-βRI kinase inhibitor SB431542, Emdogain failed to cause any significant changes in gene expression. Consistent with this mechanism, three independent TGF-βRI kinase inhibitors and a TGF-β 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-βRI kinase activity is necessary to mediate the effects of Emdogain on gene expression in vitro.
authors.affiliation: Department of Periodontology, School of Dental Medicine, University of Bern, Bern, Switzerland; Laboratory of Oral Cell Biology, School of Dental Medicine, University of Bern, Bern, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stähli
authors.affiliation: Department of Periodontology, School of Dental Medicine, University of Bern, Bern, Switzerland; Robert K. Schenk Laboratory of Oral Histology, School of Dental Medicine, University of Bern, Bern, Switzerland.
authors.forename: Dieter
authors.initials: D
authors.lastname: Bosshardt
authors.affiliation: Department of Periodontology, School of Dental Medicine, University of Bern, Bern, Switzerland.
authors.forename: Anton
authors.initials: A
authors.lastname: Sculean
authors.affiliation: Department of Periodontology, School of Dental Medicine, University of Bern, Bern, Switzerland; Laboratory of Oral Cell Biology, School of Dental Medicine, University of Bern, Bern, Switzerland.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Gruber
mesh_terms: D001483:Base Sequence; D052004:Bone Morphogenetic Protein Receptors / Q000502:physiology; D002478:Cells, Cultured; D017931:DNA Primers; D003746:Dental Enamel Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D017370:Interleukin-11 / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010159:Palate / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051900:Smad3 Protein / Q000502:physiology
chemical_list: D017931:DNA Primers; D003746:Dental Enamel Proteins; D017370:Interleukin-11; D018125:Receptors, Transforming Growth Factor beta; C497790:SMAD3 protein, human; D051900:Smad3 Protein; C109069:enamel matrix proteins; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D052004:Bone Morphogenetic Protein Receptors; D000077293:Receptor, Transforming Growth Factor-beta Type I