Figure 1.

FXR activity, ASBT localization, and taurocholic acid (TC)-dependent gene induction in the CF ileum. (A) Expression of genes involved in bile acid signaling in the ileum (Fgf15, Shp, Fxr, Asbt, Fgfr4) and liver (shaded bars; Cyp7a1, Fgfr4) of CF mice (Cftr-/-) and controls (Cftr N/N). Data represent expression in a CF animal relative to an age-/sex-matched littermate control (means ± SE). The number of couples analyzed is indicated within/above each bar. a, P = .005; b, P = 0.001; c, P = .005; ns, P > .05 (paired ratio t test). (B) Immunohistochemical detection of ASBT in ileum of CF mice (Cftr-/-) and controls (Cftr N/N). ASBT was localized at the apical aspect of epithelial cells of the villi, but was absent from crypts. (C) ASBT was detected by Western analysis in brush-border membranes prepared from CF (-/-) and control (N/N) ileum. Both the monomeric (46 kilodaltons) and dimeric form were detected. Numerals to the left of the blot refer to the molecular mass (kilodaltons) of protein standards. ASBT abundance was quantified on the basis of the immune-reactive signal of both the monomer and dimer (bar diagram). Data shown are means ± SE of 5 mice per genotype. d, P = .03 (paired t test, 2-tailed). (D) Induction of gene expression by TC in ileal tissue sections of CF mice (Cftr-/-) and controls (Cftr N/N). Data shown are means ± SE. The number of biological replicates is indicated within/above each bar. e, Two-way analysis of variance indicated that TC treatment significantly enhanced Fgf15 expression (P = .006), independent of genotype.