Relationship between high glucose-induced hepatic stellate cell activation and the p38MAPK signaling pathway

Abstract

Objective To explore the relationship between p38-mitogen activated protein kinase (p38MAPK) signaling pathway and high glucose-induced hepatic stellate cell (HSC) activation. Methods HSC was cultivated, and morphological identification was conducted. Twenty human HSC samples were randomly collected to represent each experimental group including the control group, high glucose group and blocking group. Cells from the control group were cultured under normal conditions. Cells from the high glucose group were cultured under high glucose conditions of which the ultimate concentration was 25mol/L. The blocking group was cultured under high glucose conditions in the presence of the p38MAPK inhibitor SB203580 of which the ultimate concentration was 40mol/L. After incubation for 120 h, SABC and Western blot analysis were used to detect α-SMA expression in each sample to determine the degree of hepatic stellate cell activation. Western blot analysis was also used to detect the expression of phospho-p38MAPK protein in each group. Results According to identification, the cultured HSC was flat with big cell body, and had well-developed stress fiber. There was less fat droplet in the cytoplasm. The result of SABC situ test showed that, compared with the high glucose group, positive signal of α-SMA proteins was stronger than that of control group which had similar positive signal as the blocking group. The differences of both HSCα-SMA and p-p38MAPK protein expression levels in three groups had statistical significance (F=31.36, 78.49, P all<0.01) . Among them, the expression level of α-SMA in the high glucose group was (34.61±4.07) % and higher than (23.90±6.02) % of control group and (26.48±4.41) % of blocking group, of which the differences were statistically significant (t=-7.20 and -5.37, P both <0.01) . The expression level of p-p38MAPK was (22.79±3.80) % in the high glucose group, (8.13±4.95) % in the control group and (10.66±4.15) % in the blocking group, of which the differences had statistical significance (t=-11.01 and -10.41, P both <0.01) . Conclusion The higher level of HSC represents the higher signal strength of p38MAPK. However, blocking the p38MAPK signaling pathway can reduce the activation of hepatic stellate cells. Key words: Liver cirrhosis; Hepatic stellate cells; α-SMA; p38MAPK signaling pathway