Hypoxia activates the JNK pathway to modulate fibrosis-related proteins expression. Panel A: Effect of JNK pathway inhibitor on the hypoxia-induced expression of indicated protein. Representative Western blots and levels of HIF-1α, fibrosis-related proteins (COL1A, COL3A, TGF-β1, α-SMA) and phosphorylated JNK and SEK/MKK4 in HL-1 cells that were pre-incubated with SP600125 (10−5 M) or DMSO as a vehicle for 30 min, then treated with hypoxia stress (1% O2) for 6 h. The bar graph shows the value of each sample relative to that of control cells that received vehicle only. The data are mean ± SEM (n = 4 per group, * p < 0.05 vs. control; # p < 0.05 vs. hypoxia) from four independent experiments. Panel B: Dominant-negative-JNK (DN-JNK) gene transfection attenuated hypoxia-induced COL1A, COL3A and p-JNK expression in HL-1 cells. Representative Western blots and COL1A and COL3A levels in HL-1 cells transfected with vehicle pCDN3 (CTL) or DN-JNK for 24 h before 6h-hypoxia treatment. The data are mean ± SEM (n = 3 per group, * p < 0.05 vs. control; # p < 0.05 vs. hypoxia) from three independent experiments.