Expression of PERK-eIF2α-ATF4 pathway signaling protein in the progression of hepatic fibrosis in rats.

Objective: This study aims to observe changes in the expression of the hepatic endoplasmic reticulum stress PERK-eIF2α-ATF4 signaling pathway protein in the progression of CCl-induced hepatic fibrosis in rats.

Methods: Male Wistar rats were sacrificed at the end of the 2, 4, 8 and 12 weeks, respectively. A specific test was performed to compare the pathological changes of hepatic tissues in the model and normal groups. Immunohistochemical staining and Western blot were carried out to detect the expression of p-PERK, p-eIF2α and ATF4 proteins in the hepatic tissue group. Furthermore, real-time PCR was used to detect changes in the expression of ATF4 mRNA in hepatic tissues.

Results: In the eight-week and twelve-week hepatic fibrosis group, significant fibrosis hyperplasia was identified in the livers of rats, and pseudo-lobules were also formed in the livers of rats in the twelve-week hepatic fibrosis group. Immunohistochemical staining and Western blot results indicated that the expression levels of p-PERK, p-eIF2α and the ATF4 protein in the livers of rats were significantly increased from the 8 week compared with the normal group (<0.05). Real-time PCR results revealed that the expression of ATF4 mRNA was significantly increased in hepatic tissues in the hepatic fibrosis group compared with the normal group (<0.05), and this was gradually enhanced as hepatic fibrosis progressed.

Conclusions: CCl can induce an increase in the expression of the PERK-eIF2α-ATF4 signaling protein in the development of hepatic fibrosis along with phosphorylation-mediated activation, indicating that the activation of the PERK-eIF2α-ATF4 signaling pathway may contribute to the onset and development of hepatic fibrosis by regulating downstream target genes.