The TGFβ/Smad 3-signaling pathway is involved in butyrate-mediated vitamin D receptor (VDR)-expression
✍ Scribed by Carolin Daniel; Oliver Schroder; Nadine Zahn; Tanja Gaschott; Dieter Steinhilber; Jurgen M. Stein
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 392 KB
- Volume
- 102
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Abstract
Previously, we demonstrated the pivotal role of the vitamin D receptor (VDR) in mediating the butyrate‐induced differentiation in colon cancer cells. Smad 3, a downstream component of transforming growth factor‐β (TGFβ) signaling, has been shown to act as a coactivator of VDR and to possibly regulate the vitamin D signaling pathway. In this study, we demonstrate a distinct impact of the TGFβ/Smad 3‐signaling pathway in the butyrate‐mediated VDR expression and induction of differentiation. Butyrate treatment resulted in a significant induction of the phosphorylation level of Smad 3, while the combination of butyrate and a specific TGFβ1‐antibody or a TGFβ‐receptor inhibitor considerably diminished the butyrate‐induced upregulation of VDR expression. Using a specific inhibitor, we were also able to demonstrate an involvement of the p38 MAPK in the increase of Smad 3 phosphorylation following butyrate treatment, thus opening the view to further elucidate possible mechanisms mediating the upregulation of VDR expression following butyrate treatment in colon cancer cells. J. Cell. Biochem. 102: 1420–1431, 2007. © 2007 Wiley‐Liss, Inc.