Regulation of Fgf15 expression in the intestine by glucocorticoid receptor

Abstract

Fibroblast growth factor 15 (FGF15) was previously identified to be highly expressed in the ileum and functions as an endocrine factor to regulate bile acid synthesis in the liver. FGF15 targets its receptor fibroblast growth factor receptor 4 in the liver and serves important roles in energy metabolism, including bile acid homeostasis, glucose metabolism and protein synthesis. The expression of FGF15 is known to be regulated by the transcription factor farnesoid X receptor (FXR). In the present study, reverse transcription-quantitative polymerase chain reaction was used for measuring Fgf15 expression from the animal and tissue culture experiments, and it was identified that dexamethasone, a drug widely used in anti-inflammation therapy, and a classical inducer of glucocorticoid receptor (GR)- and pregnane X receptor (PXR)-target genes, may downregulate Fgf15 expression in the ileum. GR was identified to be highly expressed in the ileum by western blot analysis. Furthermore, it was demonstrated that the downregulation of Fgf15 by dexamethasone is due to the repression of ileal FXR activity via GR; however, not PXR, in the ileum. The present results provide insight for a better understanding of the adverse effects associated with dexamethasone therapy.