Sphingosine-1-phosphate stimulated connective tissue growth factor expression in human buccal fibroblasts: Inhibition by epigallocatechin-3-gallate.

[oral submucous fibrosis]

Connective tissue growth factor (CCN 2 ) has been associated with the pathogenesis of various fibrotic diseases , including oral submucous fibrosis (OSF ). The chemical constituents of areca nut along with the mechanical trauma cause OSF . The coarse fibers of areca nut injure the mucosa and hence sphingosine-1 -phosphate (S 1 P ) is released at the wounded sites . Recent studies have shown that S 1 P is involved in wound healing and the development of fibrosis . The aims of this study were to investigate the effects of S 1 P on CCN 2 expression in human buccal fibroblasts (HBFs ) and identify the potential targets for drug intervention or chemoprevention of OSF .W estern blot analyses were used to study the effects of S 1 P on CCN 2 expression and its signaling pathways in HBFs and whether epigallocatechin-3 -gallate (EGCG ), the main and most significant polyphenol in green tea , could inhibit this pathway .S 1 P significantly enhanced CCN 2 synthesis in HBFs . This effect can be inhibited by c-Jun NH 2 -terminal kinase (JNK ) inhibitor and extracellular signal-regulated kinase inhibitor but not by P 38 mitogen-activated protein kinase inhibitor . Interestingly , EGCG completely blocked S 1 P -induced CCN 2 expression via suppressing S 1 P -induced JNK phosphorylation .S 1 P released by repetitive mechanical trauma during AN chewing may contribute to the pathogenesis of OSF through upregulating CCN 2 expression in HBFs . EGCG could be an adjuvant to the current offered therapy options or the prevention of OSF through suppression of JNK activation .