FIGURE 4.

Ivabradine, but not zatebradine, reduces JNK/p38 MAPK activation and the high glucose (HG)-induced increase in fibrogenic protein expression in vitro (A) NRCFs were pretreated with or without ivabradine at the indicated concentrations for 30 min, and then exposed to HG for 48 h. JNK and p38 MAPK phosphorylation and total JNK and p38 MAPK expression were determined by western blotting (B) NRCFs were treated as described in (A) and the protein expression of PCNA, α-SMA, TIMP2, collagen I, collagen III, and MMP2 was determined by western blotting (C and D) NRCFs were pretreated with or without zatebradine at the indicated concentrations for 30 min, and then exposed to HG for 48 h. The proteins described in (A) and (B) were quantified by western blotting (E and F) NRCFs were treated as described in (A) and (C) and the cell proliferation rate was determined using an MTT assay. Data are presented as mean ± SEM (n = 3). p-values were calculated using one-way ANOVA with Tukey multiple comparison test. *p < 0.05, compared to the normal group; ^# p < 0.05, compared to the HG group.