FIG. 7.

FXR and HA signaling crosstalk through IL-1β, TGF-β1, and H1HR. (A) IPA demonstrated a link between HA and FXR signaling crosstalk through IL-1β, TGF-β1, and H1HR. (B) TGF-β1 and IL-1β expression increased in isolated cholangiocytes from Kit^W-sh + MC compared with WT and Kit^W-sh mice by qPCR and inhibition of MC-FXR reduced biliary TGF-β1 and IL-1β expression. (C) Serum HA increases in patients with PSC (n = 14) and PSC-IBD (n = 17) compared with controls. (D) WT and Kit^W-sh have minimal HA serum secretion, which is elevated in Kit^W-sh + MC mice. (D) Serum HA is reduced in Kit^W-sh + MC-Gugg mice. (E) MC injection increases biliary H1HR expression in Kit^W-sh + MC compared with WT and Kit^W-sh mice and inhibition of MC-FXR reduces biliary H1HR expression. Data are mean ± SEM of n = 8 experiments for qPCR, n = 4 experiments for HA EIA from 6–8 mice per group, and n = 2 experiments per patient sample for HA EIA. *P < 0.05 vs. control group, #P < 0.05 vs. Kit^W-sh + MC. Abbreviation: Inj, injury.