To explore the effect of microRNA-377-3p (miR-377-3p) on autophagy and apoptosis in acute liver failure (ALF) through fibroblast growth factor receptor 1 (FGFR1).

D-galactosamine (D-GalN)/lipopolysaccharide and D-GalN/tumor necrosis factor-alpha (TNF-α) were respectively used to induce ALF animal models and cell apoptosis models. Twelve C57BL/6J mice were divided into a control group and a model group, with six mice in each group. Cells were divided into a control group, a model group (induced by D-GalN and TNF-α), a NC mimic group (induced by D-GalN and TNF-α and transfected with nonsense miRNA control sequence), a miR-377-3p mimic group (induced by D-GalN and TNF-α and transfected with miR-377-3p mimics) and a miR-377-3p mimic + 3-MA group (induced by D-GalN and TNF-α and transfected with miR-377-3p mimics while applying autophagy inhibitor 3-MA intervention). The pathology of liver tissue, the serum levels of biochemical parameters, apoptosis-related proteins, autophagy-related proteins and the cellular expression levels of miR-377-3p RNA, autophagy-related proteins, FGFR1 protein were examined in each group. The targeted binding relationship between miR-377-3p and FGFR1 was measured by dual-luciferase reporter gene experiment and apoptosis was determined by flow cytometry.

Hematoxylin-eosin staining showed that the hepatocytes around the central vein of the control group were arranged radially, and there was no inflammatory cell infiltration. In the model group, the structure of hepatic lobule was destroyed, a large number of liver cells were necrotic, and surrounding inflammatory cells were infiltrated. There were significant differences in the apoptosis rate and expressions of autophagy proteins Beclin-1, LC3Ⅱ/Ⅰ and p62 in the five groups (F = 88.520, 42.760, 95.870, 62.930; all P < 0.001). Compared with the model group, the apoptosis rate and p62 protein level of the miR-377-3p mimic group were significantly decreased, while the levels of Beclin-1 and LC3Ⅱ/Ⅰ were significantly increased (all P < 0.05). The FGFR1 protein expression levels were significantly different in the control group, model group, NC mimic group and miR-377-3p mimic group (F = 84.670, P < 0.001). The FGFR1 expression level in the miR-377-3p mimic group was significantly decreased compared with the model group (P < 0.05). There were statistically significant differences in the expression levels of autophagy related proteins Beclin-1, LC3Ⅱ/Ⅰ and p62 in the control group, model group, miR-377-3p mimic group, miR-377-3p mimic + NC group (induced by D-GalN and TNF-α and transfected with miR-377-3p mimics and blank vectors) and miR-377-3p mimic + FGFR1 group (induced by D-GalN and TNF-α and transfected with miR-377-3p mimics and FGFR1 target sequence vectors) (F = 63.840, 61.590, 127.800; all P < 0.001). Compared with the miR-377-3p mimic group, Beclin-1 and LC3Ⅱ/Ⅰ levels in the miR-377-3p mimic + FGFR1 group were decreased, while p62 protein levels were increased (all P < 0.05).

MiR-377-3p negatively regulates the FGFR1 expression and enhances the autophagy level in L02 cells to reduce the apoptosis induced by D-GalN/TNF-α and exert the protective effect for ALF.