Abstract: Objective To determine whether JNK signaling pathway is involved in high glucose (HG)-induced proliferation of cardiac fibroblasts (CFs) in rats. Methods Rat CFs were cultured in DMEM (NG: 5.5 mmol/L D-glucose; HG: 12, 18, 25 mmol/L D-glucose; OSM: 5.5 mmol/L D-glucose + 19.5 mmol/L mannitol) for indicated time periods (0, 12, 24, 48 h). Meanwhile, Rat CFs were cultured in DMEM (25 mmol/L D-glucose) with SP600125 (10, 20 μmol/L), a JNK inhibitor, for 48 h. Proliferation was measured by MTT. The expression of proliferating cell nuclear antigen (PCNA), total JNK and phosphorylation of JNK were detected by Western blot analysis. c-jun mRNA expression was assessed by RT-PCR. Results Treatment of CFs with HG significantly increased phosphorylation of JNK in time- and glucose concentration-dependent manner. Compared with NG group, exposure of CFs to HG (25 mmol/L) significantly promoted the proliferation of CFs (0.44±0.02 vs 0.31±0.02, P<0.01), and upregulated c-jun mRNA expression and PCNA levels. SP600125 significantly suppressed HG-induced the proliferation of CFs and the activity of JNK in a dose-dependent manner. Conclusions HG stimulates the proliferation of CFs partially through JNK pathway activation.

Key words: Keywords: glucose, cardiac fibroblasts, proliferation, c-jun N-terminal kinase pathway