THE PROTECTIVE ROLE OF GP96 IN THE PROCESS OF ACUTE ALCOHOLIC LIVER INJURY

Ying Song^{1, 2, 3}, Huan Yang^{1, 3}, San-Qiang Li^{1, 3, *}, Meng-Li Yang^{1, 3}, Ping Wang^{1, 3}

¹The molecular medicine key laboratory of liver injury and repair, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang - ²The Second Affiliated Hospital of Henan University of Science and Technology, Luoyang - ³Henan Center for Engineering and Technology Research on Prevention and treatment of liver Diseases, Luoyang, People’s Republic of China

Introduction: More and more attention has been paid to the expression of heat shock protein Gp96 in anti-infective immunity, tumorigenesis and development. However, the impact of Gp96 on alcoholic liver injury remains unclear. 

Materials and methods: The single guider RNA (sgRNA) targeting Gp96 sequences were designed using CRISPR/Cas9 technology and injected into mice via tail vein, then the mice were ingested alcohol one-time via oral gavage. Twenty four hours later, the pathological changes of liver in mice were detected by Hematoxylin-eosin, periodic acid-schiff and Hoechst 33258 staining. The expression of related proteins was detected by Western blotting. 

Results: The livers in sgRNA3-injected mice showed more obvious hepatocyte necrosis and inflammatory cell infiltration (P<0.01), more severe hepatocyte apoptosis (P<0.05) and glycogen consumption (P<0.01) than saline-injected mice after alcohol administration. Compared with saline-injected mice, the expression levels of CYP2E1, Bax, Caspase 3 and TNF-α in sgRNA3-injected mice hepatocytes were significantly higher (P<0.05 or P<0.01), while the expression levels of Gp96, HSP27, HSP70, p-STAT3, PCNA, VEGF and Bcl-2 were significantly lower (P<0.05 or P<0.01). 

Conclusion: Inhibition of Gp96 could significantly aggravate alcohol-induced acute liver injury and Gp96 might play protective role during alcohol-induced acute liver injury by regulating related genes expression.