The role of glucagon-like peptide-1 receptor agonist on the promotion of hepatic stellate cell apoptosis through JNK signaling pathway

Abstract

Objective To explore the mechanism of glucagon-like peptide-1 receptor agonist (GLP-1RA) promoting the apoptosis of hepatic stellate cells (HSC) through the JNK signaling pathway. Methods The HSC were cultured in vitro and applied morphological identification. HSC samples were divided into control group (20 samples) , GLP-1RA group (20 samples) and JNK signaling pathway blocking group (20 samples) . The control group was cultured with high glucose (final concentration of 25 mmol/L) . The GLP-1RA group was added GLP-1RA-Liraglutide (final concentration of 10 mmol/L) based on the control group. The JNK blocking group was added JNK signaling pathway blocker SP600125 (final concentration of 20 μmol/L) based on the GLP-1RA group. After 120 hours, the apoptosis of HSC in each group was detected by flow cytometry. The expression levels of p-JNK protein were determined by Western blotting. Results The differences of apoptosis rates of HSC and the expression levels of p-JNK protein in three group were statistically significant (F=19.412 and 66.451, P both <0.01) . The apoptosis rate of HSC and the expression level of p-JNK protein in GLP-1RA group were (30.61±4.07) % and (22.79±3.80) %, which were both higher than control group with significant differences (t=0.530 and 9.854, P both <0.01) . The apoptosis rate of HSC and the expression level of p-JNK protein in JNK signaling pathway blocking group were (23.48±4.41) % and (10.66±4.15) %, which were both lower than GLP-1RA group with significant differences (t=-5.428 and-8.757, P both <0.01) . Conclusions JNK signaling pathway plays a key role in the GLP-1RA mediated apoptosis of HSC. GLP-1RA can promote the apoptosis of high glucose-induced HSC through JNK signaling pathway. Key words: Apoptosis; Hepatic stellate cells; JNK signaling pathway