ABSTRACT.The relationship between the p38-mitogen-activated protein kinase (p38-MAPK) signal pathway and high glucose-induced hepatic stellate cell (HSC) activation was investigated in this study. Sixty human HSC samples were randomly selected and used in the control (cultured normally), high-glucose (cultured in the presence of high glucose), and blocking (cultured under high-glucose conditions in the presence of the p38-MAPK inhibitor, SB203580) groups. The cells were incubated for 120 h and subsequently analyzed for morphological changes by inverted microscopy and for a-smooth muscle actin (a-SMA) expression (to determine the degree of HSC activation) by the method of streptavidin-biotin complex and western blot. Phospho-p38-MAPK protein expression was analyzed by western blotting. a-SMA and phospho-p38-MAPK expression was significantly upregulated in HSCs cultured under high-glucose conditions, compared to the HSCs cultured normally (P < 0.01). On the other hand, phospho-p38-MAPK and a-SMA protein levels were significantly lower in the blocking group compared to the high-glucose group (P < 0.01). Based on these results, we concluded that high-glucose levels induce HSC activation mediated by phospho-p38-MAPK. Therefore, blocking the p38-MAPK signal pathway could inhibit this effect.

This study aimed to investigate the stimulatory effect of glucagon-like peptide 1 (GLP-1) receptor agonist (GLP-1RA) on the apoptosis of hepatic stellate cells (HSCs) activated by high glucose, and to explore the underlying molecular mechanism with a focus on the c-Jun N-terminal kinase (JNK) and extracellular signal-related kinase (ERK) signaling pathways. Human HSCs were cultured in-vitro and their morphological features were identified. HSC samples were randomly collected and divided into a control group, GLP-1RA group, GLP-1RA+JNK blockade group, and ERK blockade group. The apoptosis of HSCs in each group were analyzed by fluorescence-activated cell sorting (FACS) after 120 h of culture. Phosphorylated JNK and ERK (p-JNK and pERK) Bingbing Zhang, et al. 2 Genetics and Molecular Research 16 (4): gmr16039818 proteins were detected by western blotting. p-JNK expression was higher in the GLP-1RA group compared with that of the control group and the GLP-1RA+JNK blockade group (both P<0.01). The apoptosis rate was higher in the GLP-1RA group compared with that of the control group and GLP-1RA+JNK blockade group (both P<0.01). pERK expression was lower in the GLP-1RA group and ERK blockade group than in the control group (both P<0.01). The apoptosis rates in the GLP-1RA group and ERK blockade group were higher than that of the control group (both P<0.01). GLP-1RA can promote the apoptosis of high glucose-activated HSCs through activation of the JNK signal pathway and through blocking the ERK signal pathway.