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Curcumin inhibits TGFβ1-induced CCN2 via Src, JNK, and Smad3 in gingiva

W-H Yang1, M Y-P Kuo, C-M Liu

  • 1School of Dentistry and Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.

Journal of Dental Research
|April 24, 2013
PubMed

Insights

Transforming growth factor β (TGFβ) activates connective tissue growth factor (CCN2) in gingival overgrowth. Src kinase mediates this TGFβ-induced CCN2 expression, and curcumin inhibits this pathway, suggesting potential GO treatment.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Oral Pathology

Background:

  • Transforming growth factor β (TGFβ) is implicated in gingival overgrowth (GO) pathogenesis.
  • Connective tissue growth factor (CTGF/CCN2) is overexpressed in GO and sustains TGFβ-initiated fibrosis.
  • JNK and Smad3 activation are known mediators of TGFβ-induced CCN2 expression in human gingival fibroblasts (HGFs).

Purpose of the Study:

  • To investigate the role of Src kinase in TGFβ-induced CCN2 expression in HGFs.
  • To determine if Src acts upstream of JNK and Smad3 in this signaling pathway.
  • To evaluate the potential of curcumin as an inhibitor of TGFβ-induced CCN2 expression and related cellular responses in HGFs.

Main Methods:

  • Human gingival fibroblasts (HGFs) were treated with TGFβ1.
  • Src kinase inhibitors (PP2, Src inhibitor-1) were used to assess Src's role.
  • Western blotting was employed to analyze protein phosphorylation (Src, JNK, Smad3) and CCN2 expression.
  • Cell migration and α-SMA expression assays were performed.

Main Results:

  • TGFβ1 significantly increased CCN2 expression in HGFs.
  • Src kinase inhibitors markedly reduced TGFβ1-induced CCN2 synthesis and JNK/Smad3 activation.
  • Curcumin treatment inhibited TGFβ1-induced phosphorylation of Src, JNK, and Smad3, and abrogated CCN2 expression.
  • Curcumin also suppressed TGFβ1-induced HGF migration and α-SMA expression.

Conclusions:

  • Src is a critical upstream signaling mediator for TGFβ1-stimulated CCN2 expression in HGFs, acting upstream of JNK and Smad3.
  • Curcumin effectively inhibits the TGFβ1/Src/JNK/Smad3 signaling pathway in HGFs.
  • Curcumin demonstrates potential as a therapeutic agent for controlling gingival overgrowth by mitigating fibrosis and cellular responses.
Keywords:
CTGF/CCN2TGFβ1connective tissue growth factorcurcumingingival overgrowthtransforming growth factor β

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