Curcumin Inhibits TGF-β-induced CTGF Expression in Human Gingival Fibroblasts
Date Issued
2010
Date
2010
Author(s)
Chen, Jung-Tsu
Abstract
Many fibrotic pathologies are associated with increasing levels of TGF-β. TGF-β not only increases synthesis of matrix proteins but also enhances secretion of protease inhibitors while reducing secretion of proteases and resulted in matrix accumulation. Connective tissue growth factor (CTGF) belongs to CCN family and is a cysteine-rich polypeptide. It acts as a down stream profibrotic effector of TGF-β and has been proved to be associated with the onset and progression of fibrosis in many human tissues. Curcumin, a yellow pigment from turmeric, has been shown to reduce matrix accumulation in pulmonary and hepatic fibrosis. Objectives: One of the purposes of this study is to compare CTGF expression between normal gingival tissue and overgrowth gingival tissue. The other one is to investigate the inhibition effect of curcumin in TGF-β induced CTGF expression in normal primary human gingival fibroblasts. Methods: Tissue specimens from 7 cases of gingival overgrowth were examined by immunohistochemistry with the expression of CTGF protein. Healthy gingival tissues were obtained from patients under treatment of odontectomy. Gingival fibroblasts were isolated by collagenase/dispase digestion method and used for the subsequent analysis in the third passage. The effect of curcumin on cell viability was tested by MTT assay. Gingival fibroblasts were stimulated with 5 ng/mL TGF-β1 and the effects of curcumin (10 μM) on TGF-β1 induced CTGF gene and CTGF protein, TGF-β1 receptors protein, phosphorylated Smad2/3 proteins and MAPK proteins expression were analyzed by RT-PCR and western blotting. Results: Drug-induced gingival overgrowth was found with positive CTGF staining in epithelial cells, fibroblasts, endothelial cells and smooth muscle cells. Curcumin was nontoxic at doses of 0 to 10 μM. Pre-treatment with curcumin one hour before TGF-β1 stimulation demonstrated that curcumin reduced CTGF expression. Curcumin also attenuated the phorsphorylation of Smad2/3, MAPK and translocation of Smad2 induced by TGF-β1. Interruption of MAPK signaling by inhibitors did not reduce the CTGF expression. Conclusion: It is concluded that curcumin suppressed TGF-β1-induced CTGF expression probably through the interruption of Smad2/3 signaling. Further study for application of curcumin in clinical treatment is suggested.
Subjects
gingival overgrowth
TGF-β
CTGF
curcumin
SDGs
Type
thesis
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