RESUMO
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.
Assuntos
Actinas/genética , Glucose/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Actinas/agonistas , Actinas/antagonistas & inibidores , Actinas/metabolismo , Células Cultivadas , Regulação da Expressão Gênica , Glucose/metabolismo , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/metabolismo , Humanos , Imidazóis/farmacologia , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
We investigated the effects of glucagon-like peptide-1 receptor (GLP-1R) agonists on p38 mitogen-activated protein kinase (MAPK) signaling during inhibition of hepatic stellate cell (HSC) activity. Human HSCs were cultured and morphologically identified. HSC samples were collected and randomly divided into three groups (N = 20 samples per group): a control group treated with high glucose (final concentration 25 mM); a GLP-1R agonist group treated with liraglutide (final concentration 5 mM); and a p38-blocked group treated with the p38 MAPK inhibitor SB203580 (final concentration 14 µM). All cells were cultured for 120 h followed by detection of phosphorylated p38 MAPK (p-p38 MAPK) and α-smooth muscle actin (α-SMA, a measure of HSC activation) by western blot. p-p38 MAPK and α-SMA expression levels were both significantly lower in HSCs in the GLP-1R agonist and p38-blocked groups compared with the control group (all P < 0.01). GLP-1R agonists may inhibit the activation of HSCs by blocking the p38 MAPK signaling pathway.