Figure 5.

Activation of the JNK signaling cascade by FGF-19 causes suppression of CYP7A1. (A) Primary cultures of human hepatocytes were treated with FGF-19 (80 ng/mL) alone or in combination with the JNK inhibitor SP600125 (10 μM). SP600125 was added to the culture medium as a 1000× stock in DMSO 30 min before the addition of recombinant FGF-19. Control cultures received vehicle (0.1% DMSO) alone. Cells were cultured for a further 6 h prior to harvest, and Northern blot analysis of CYP7A1 and β-actin expression. (B) FGF-19 activates the JNK-signaling cascade. Total cell lysates were prepared from hepatocytes treated for 3 h as described above. The level of activated c-Jun was analyzed by immunoblotting using antibodies specific for Ser 63-phosphorylated c-Jun. Data are representative of a least three individual hepatocyte preparations.