ALK5 inhibition blocks TGFß-induced CCN2 expression in gingival fibroblasts

K Thompson, D W Hamilton, A Leask
Journal of Dental Research 2010, 89 (12): 1450-4
Connective tissue growth factor (CCN2/CTGF) is not normally expressed in gingival fibroblasts, but is induced by the potent profibrotic cytokine TGFβ and is overexpressed in gingival fibrosis. Since CCN2 is a marker and mediator of fibrosis, targeting CCN2 expression in gingival fibroblasts may provide new insights into the future development of novel therapeutic opportunities to treat oral fibrosis. Herein we used real-time polymerase chain-reaction, Western blot, and indirect immunofluorescence analysis to evaluate whether SB-431542, a specific pharmacological inhibitor of TGFβ type I receptor (ALK5), blocks the ability of TGFβ to induce CCN2 mRNA and protein expression in human gingival fibroblasts. Our results indicate that CCN2 mRNA and protein are induced by TGFβ in gingival fibroblasts in a SB-431542-sensitive fashion. These results suggest that blocking ALK5 may be useful in blocking the profibrotic effects of TGFβ in gingival fibroblasts.

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