PuSH - Publication Server of Helmholtz Zentrum München: p38 MAPK signaling pathway is involved in butyrate-induced vitamin D receptor expression.

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Daniel, C.* ; Schröder, O.* ; Zahn, N.* ; Gaschott, T.* ; Stein, J.*

p38 MAPK signaling pathway is involved in butyrate-induced vitamin D receptor expression.

Biochem. Biophys. Res. Commun. 324, 1220-1226 (2004)

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Previously, we have demonstrated that the butyrate-induced differentiation in the human colon cancer cell line Caco-2 occurs via upregulation of the vitamin D receptor (VDR). However, the downstream pathways involved are unknown. The mitogen-activated protein kinases (MAPKs) have been shown to play an important role in regulation of cell differentiation, and may therefore be a potential target of butyrate action. To assess their role in butyrate-mediated cell differentiation and VDR expression, we used the specific p38-MAPK inhibitor SB203580 and the ERK1/2 MAPK-inhibitor PD98059. The p38-MAPK inhibitor abolished the butyrate effect on VDR expression and cell differentiation, while the ERK1/2 inhibitor did not influence the butyrate-mediated induction of cell differentiation and VDR expression. The essential role of the p38 pathway in up-regulation of VDR expression was further confirmed by using the p38 stimulator arsenite. These results imply an important role of the p38-MAPK in regulation of cellular differentiation through upregulation of VDR expression by butyrate.

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