Curcumin inhibits thrombin-stimulated connective tissue growth factor (CTGF/CCN2) production through c-Jun NH2-terminal kinase suppression in human gingival fibroblasts
Journal
Journal of Periodontology
Journal Volume
83
Journal Issue
12
Pages
1546-1553
Date Issued
2012
Author(s)
Abstract
Background: Connective tissue growth factor (CTGF/CCN2), associated with multiple human fibrotic diseases, is overexpressed in the tissue of gingival overgrowth. Although surgical excision is the current treatment modality for gingival overgrowth, the recurrent rate is high despite proper recall programs. Thrombin plays a key role in wound repair, remodeling, and fibrosis after injury and exerts profibrotic effects by activating protease-activated receptors (PARs). Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1, 6-heptadiene-3,5-dione] is a natural plant phenolic compound that possesses both anti-inflammatory and antioxidant properties. This study investigates the signaling pathway of thrombininduced CCN2 expression and inhibition of CCN2 expression by curcumin. Methods: The signaling pathway of thrombin-induced CCN2 expression in human gingival fibroblasts (HGFs) was studied using Western blot analysis. The CCN2 mRNA level was determined by quantitative reverse transcription-polymerase chain reaction. Results: Thrombin induced CCN2 expression in HGFs by activating PAR1. Pretreatment with antioxidant N-acetyl-L-cysteine, apoptosis signal-regulating kinase 1 (ASK1) inhibitor thioredoxin, and c-Jun NH2-terminal kinase (JNK) inhibitor SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) significantly reduced thrombin-induced CCN2 expression in HGFs. Curcumin dose dependently inhibited thrombin-induced CCN2 expression through JNK suppression in HGFs. Conclusions: The results of this study suggest that thrombininduced CCN2 expression may occur through PAR1, reactive oxygen species, ASK1, and JNK signaling in HGFs. Curcumin could effectively inhibit CCN2 expression through JNK suppression. These signaling events are important for wound healing and fibrosis. Additional research, including animal studies, is required to confirm the inhibiting role of curcumin in the development of gingival overgrowth. ? 2012 American Academy of Periodontology.
SDGs
Other Subjects
apoptosis signal regulating kinase 1; connective tissue growth factor; curcumin; enzyme inhibitor; proteinase activated receptor; reactive oxygen metabolite; stress activated protein kinase; thrombin; article; biosynthesis; cell culture; cytology; drug antagonism; drug effect; enzyme activation; fibroblast; gingiva; gingiva overgrowth; human; metabolism; physiology; signal transduction; Cells, Cultured; Connective Tissue Growth Factor; Curcumin; Enzyme Activation; Enzyme Inhibitors; Fibroblasts; Gingiva; Gingival Overgrowth; Humans; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase Kinase 5; MAP Kinase Signaling System; Reactive Oxygen Species; Receptors, Proteinase-Activated; Thrombin
Type
journal article