The TGF beta/Smad 3-signaling pathway is involved in butyrate-mediated vitamin D receptor (VDR)-expression
Daniel, C; Schroder, O; Zahn, N; Gaschott, T; Steinhilber, D; Stein, JM
| HERO ID | 1458715 |
|---|---|
| In Press | No |
| Year | 2007 |
| Title | The TGF beta/Smad 3-signaling pathway is involved in butyrate-mediated vitamin D receptor (VDR)-expression |
| Authors | Daniel, C; Schroder, O; Zahn, N; Gaschott, T; Steinhilber, D; Stein, JM |
| Journal | Journal of Cellular Biochemistry |
| Volume | 102 |
| Issue | 6 |
| Page Numbers | 1420-1431 |
| 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-beta (TGFbeta) 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 TGFbeta/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 TGFbeta1-antibody or a TGFbeta-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. |
| Doi | 10.1002/jcb.21361 |
| Pmid | 17471513 |
| Wosid | WOS:000251433900009 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000251433900009 |
| Is Public | Yes |
| Language Text | English |
| Keyword | butyrate; short chain fatty acids; vitamin D receptor; transforming growth factor-beta; Smads; cellular differentiation; colon cancer cells |