Glucose regulated protein 78 is potentially an important player in the development of nonalcoholic steatohepatitis

Abstract

Endoplasmic reticulum stress (ERS) plays an important role in metabolic diseases. Glucose regulated protein 78 (GRP78) is a molecular chaperone in the ER where it is a marker for ERS activation. This study investigates the role of GRP78 in the pathogenesis of nonalcoholic steatohepatitis (NASH) in rats. Our rat model of NASH was induced by both a high sucrose and a high fat diet. The expression levels of LPS, ALT, FFA, and TG in the serum and FFA, TG, MDA, and TNFα in the liver were assessed. H&E, TUNEL and IHC staining were performed to examine histological changes, apoptosis and macrophage infiltration in the NASH liver tissue, respectively. The expression level of GRP78 in the liver was evaluated by Western blot and RT-PCR. The plasma levels of LPS, ALT, FFA, and TG in and the contents of FFA, TG, TNFα, and MDA in the liver were gradually increased. Macrophage infiltration and hepatocytic apoptosis was significantly increased in the livers of the rats from the NASH group compared to the control group. The protein and mRNA levels of GRP78 in the liver of rats from the NASH group were also upregulated. In addition, GRP78 expression levels were positively correlated with the levels of ALT, TNFα, CD68 and hepatocytic apoptosis. Thus, our results suggest that GRP78 may be an important player in the pathogenesis of NASH.