Curcumin Inhibits TGF1-induced CCN2 via Src, JNK, and Smad3 in Gingiva

Transforming growth factor (TGF) 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 TGF. Previous studies have shown that JNK and Smad3 activation is required for TGF-induced CCN2 expressions in human gingival fibroblasts (HGFs). In this study, we have found that Src is a major signaling mediator for TGF-induced CCN2 expressions in HGFs. Pre-treatment with 2 Src kinase inhibitors (PP2, Src inhibitor-1) significantly reduced TGF1-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 TGF1-stimulated CCN2 expression in HGFs. We further found that curcumin significantly abrogated the TGF1-induced CCN2 in HGFs by inhibiting the phosphorylations of Src, JNK, and Smad3. Furthermore, curcumin inhibited TGF1-induced HGF migration and -SMA expression. Curcumin potentially qualifies as a useful agent for the control of GO.