Sphingosine 1-Phosphate Stimulated Connective Tissue Growth Factor in Oral Mucosal Fibroblasts: Modulation by EGCG
Date Issued
2012
Date
2012
Author(s)
Tsai, Yi-Shin
Abstract
Connective tissue growth factor (CTGF) overexpression has been widely shown to be associated with many human diseases such as pulmonary, renal, hepatic, and gingival fibrosis. OSF is the result of persistent chemical irritation and microtrauma to oral mucosa from areca nut (AN). Previous immunohistochemical studies showed overexpression of CTGF protein in OSF tissues. In vitro study showed that arecoline enhanced CTGF expression in normal buccal mucosa fibroblasts.
Sphingosine-1-phosphate (S1P) is a low-molecular weight lysophospholipid (LPL) stored in platelets. S1P is released by platelets upon stimulation and was engaged in wound healing and coagulation process by decreasing vascular permeability and enhancing vascular stabilization. S1P is elevated in patients with IPF (idiopathic pulmonary fibrosis), correlates with the lung function and mediates EMT (epithelial to mesenchymal transition). Recent evidence suggests that S1P also plays an important role in renal fibrosis, pulmonary fibrosis and liver fibrosis. Microtrauma could lead to the release of S1P.
In our study, S1P can induce CTGF overexpression in normal buccal mucosa fibroblasts in a time- and dose-dependent manner and can be inhibited by JNK inhibitor SP600125. We also find green tea extracts, EGCG, can down-regulate CTGF expression by attenuating JNK pathway.
In the future, our expectation is to find out a drug that can reverse or inhibit the fibrotic process during the development of oral submucous fibrosis.
Subjects
oral submucous fibrosis
sphingosine-1-phosphate
connective tissue growth factor
epigallocatechin-3-gallate
SDGs
Type
thesis
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