Accumulating data demonstrated that hepatic endoplasmic reticulum (ER) stress was involved in the pathogenesis of
liver fibrosis. Long-term chronic hepatocyte death contributed to
liver fibrosis initiation and progression. Previous researches reported that ER stress sensor
inositol-requiring
enzyme 1 alpha (IRE1α) was first activated in the process of
liver fibrosis.
STF-083010 was an IRE1α
RNase specific inhibitor. This study aimed to explore the effects of
STF-083010 on
carbon tetrachloride (CCl4)-induced liver injury and subsequent
liver fibrosis. Mice were intraperitoneally (i.p.) injected with CCl4 (0.15 ml/kg) for 8 weeks. In STF-083010+CCl4 group, mice were injected with
STF-083010 (30 mg/kg, i.p.), twice a week, beginning from the 6th week after CCl4 injection. CCl4 treatment markedly enhanced the levels of serum ALT, TBIL, DBIL and TBA, and
STF-083010 had obviously extenuated CCl4-induced exaltation of ALT, DBIL, and TBA levels. CCl4-induced hepatic
hydroxyproline and
collagen I, major indicators of
liver fibrosis, were alleviated by
STF-083010. Additionally, CCl4-induced α-smooth muscle actin, a marker for hepatic stellate cells activation, was obviously attenuated in STF-083010-treated mice. Moreover, CCl4-induced upregulation of inflammatory
cytokines was suppressed by
STF-083010. Mechanistic exploration found that hepatic miR-122 was downregulated in CCl4-treated mice. Hepatic MCP1, CTGF, P4HA1, Col1α1, and Mmp9, target genes of miR-122, were upregulated in CCl4-treated mice. Interestingly,
STF-083010 reversed CCl4-induced hepatic miR-122 downregulation. Correspondingly,
STF-083010 inhibited CCl4-induced upregulation of miR-122 target genes. This study provides partial evidence that
STF-083010 alleviated CCl4-induced liver injury and thus protected against
liver fibrosis associated with hepatic miR-122.