title: Curcumin inhibits TGFβ1-induced CCN2 via Src, JNK, and Smad3 in gingiva.
abstract: Transforming growth factor β (TGFβ) is a key regulator associated with the pathogenesis of gingival overgrowth (GO). Connective tissue growth factor (CTGF/CCN2) is overexpressed in GO tissues. CCN2 promotes and sustains fibrosis initiated by TGFβ. Previous studies have shown that JNK and Smad3 activation is required for TGFβ-induced CCN2 expressions in human gingival fibroblasts (HGFs). In this study, we have found that Src is a major signaling mediator for TGFβ-induced CCN2 expressions in HGFs. Pre-treatment with 2 Src kinase inhibitors (PP2, Src inhibitor-1) significantly reduced TGFβ1-induced CCN2 synthesis and JNK and Smad3 activation in HGFs. These results suggest that Src is an upstream signaling transducer of JNK and Smad3 with respect to TGFβ1-stimulated CCN2 expression in HGFs. We further found that curcumin significantly abrogated the TGFβ1-induced CCN2 in HGFs by inhibiting the phosphorylations of Src, JNK, and Smad3. Furthermore, curcumin inhibited TGFβ1-induced HGF migration and α-SMA expression. Curcumin potentially qualifies as a useful agent for the control of GO.
authors.affiliation: School of Dentistry and Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: W-H
authors.initials: WH
authors.lastname: Yang
authors.forename: M Y-P
authors.initials: MY
authors.lastname: Kuo
authors.forename: C-M
authors.initials: CM
authors.lastname: Liu
authors.forename: Y-T
authors.initials: YT
authors.lastname: Deng
authors.forename: H-H
authors.initials: HH
authors.lastname: Chang
authors.forename: J Z-C
authors.initials: JZ
authors.lastname: Chang
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000037:antagonists & inhibitors*; D003474:Curcumin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D005419:Flavonoids / Q000494:pharmacology; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D019214:Gingival Overgrowth / Q000473:pathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008148:Lovastatin / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D051900:Smad3 Protein / Q000037:antagonists & inhibitors*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
chemical_list: C412373:AG 1879; D000873:Anthracenes; D000894:Anti-Inflammatory Agents, Non-Steroidal; C526317:CCN2 protein, human; D004791:Enzyme Inhibitors; D005419:Flavonoids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011743:Pyrimidines; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; C432165:pyrazolanthrone; D002392:Catechin; D008148:Lovastatin; C045651:epigallocatechin gallate; D019061:src-Family Kinases; D048670:MAP Kinase Kinase 4; D003474:Curcumin; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: CTGF/CCN2; TGFβ1; connective tissue growth factor; curcumin; gingival overgrowth; transforming growth factor β