Figure 4
In vitro response to OCA in both quiescent and activated, both primary murine and human LX2 HSC lines.
(A) The expression of pro-inflammatory and pro-fibrotic cytokines is unaltered in both quiescent freshly collected, as well as 7-day culture-activated HSC upon stimulation in vitro with 0.1–10 μM OCA. (B) OCA does not alter the expression of MCP-1 or MMP-13 in primary HSC stimulated with LPS or TNF-α. (C) In the human HSC line LX2, stimulation with 1 mg/mL TGF-β1 induces the expression of α-SMA and col1a1, which cannot be prevented by co-stimulation with OCA; with the exception of col1a1 expression at 10 μM OCA. (D) OCA does not affect the in vitro fraction of apoptotic LX2 cells, neither in basic nor 0.1 mg/ml TGF-β stimulated conditions. FXR, Farnesoid-X receptor; SHP, small heterodimer partner; α-SMA, alpha-smooth muscle actin; qHSC, quiescent hepatic stellate cell, aHSC, activated hepatic stellate cell; OCA, obeticholic acid; RT-PCR, reverse-transcriptase polymerase chain reaction; col1a1, collagen type I; MCP-1, monocyte chemo-attractant protein-1; PDGF-R, platelet-derived growth factor-beta receptor; TGF-β, transforming growth factor-β; IFN-γ, interferon-gamma; MMP-13, matrix metallopeptidase 13; TNF-α, tumor necrosis factor-alpha; LPS, lipopolysaccharides.
