Fig. 4.
OCA simultaneously induces miR-22, as well as FGF21, FGFR1, and PGC1α in liver cells.
Inhibiting miR-22 enhances OCA-induced FGF21 signaling leading to AMPK and ERK1/2 activation. miR-22, FGF21, FGFR1, and PGC1α mRNA (A) and protein (B) levels in Huh7 cells treated with DMSO or OCA for 6 h. (C) Protein levels in Huh7 cells infected with adenovirus negative control or the miR-22 inhibitor followed by DMSO or OCA (5 μM) treatment for 6 h. (D) miR-22 as well as the indicated mRNA levels in PHHs treated with DMSO or OCA for 6 h. (E) Indicated mRNA levels in PHHs infected with adenovirus negative control or the miR-22 inhibitor followed by DMSO or OCA (5 μM) treatment for 6 h. RT-PCR was performed in triplicate for each sample. PHHs were isolated from 1 donor liver. Data are presented as the mean ± SD (n = 3). One-way ANOVA with Tukey’s t test. ∗p <0.05, ∗∗p <0.01, ∗∗∗p <0.001. OCA, obeticholic acid; PHHs, primary human hepatocytes; RT-PCR, reverse transcription PCR.