Effect of HBx on inflammation and mitochondrial oxidative stress in mouse hepatocytes

Abstract

Hepatitis B virus x protein (HBx) serves an important role in the pathogenesis of the hepatitis B virus infection. Previous studies have reported that the interaction between HBx and hepatocyte mitochondria is an important factor leading to liver cell injury and apoptosis, ultimately inducing the formation of liver cancer. In the present study, a mouse model expressing HBx was constructed using hydrodynamic in vivo transfection based on the interaction between HBx and cytochrome c oxidase (COX) subunit III. The specific mechanism of HBx-induced oxidative stress in mouse hepatocytes and the subsequent effect on mitochondrial function and inflammatory injury was assessed. The results demonstrated that HBx reduced the activity of COX and the expression of superoxide dismutase and upregulated the expression of malondialdehyde, NF-κB and phospho-AKT, thus increasing oxidative stress. In addition, HBx induced an increase in interleukin (IL)-6, IL-1β and IL-18 expression levels, which created an inflammatory microenvironment in the liver, further promoting hepatocyte inflammatory injury. Therefore, it was proposed that HBx may affect hepatocyte mitochondrial respiration by reducing the activity of cytochrome c oxidase, leading to mitochondrial dysfunction and inducing hepatocyte inflammation and injury.

Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to PPARA agonism and fasting

“…These changes are coupled to an increase in oxidative stress 64 . Oxidative stress is known to stimulate NLRP3 inflammasome activation and IL1B maturation 22 – 24 , 65 , 66 . Interestingly, differential gene expression and pathway analysis of RNA-sequencing data in wild-type mice treated solely with WY-14643 revealed activation of some acute inflammatory response pathways.…”

Hepatitis B x antigen (HBx) is an important therapeutic target in the pathogenesis of hepatocellular carcinoma

“…Under these conditions, HBx positive cells regenerate more readily than uninfected hepatocytes, which may explain the strong association between HBx expression and the severity of CLD [ 40 , 56 ]. This also provides an evolutionary advantage by supporting a reservoir of infected cells that continue to replicate virus and maintain the carrier state even after repeated immune mediated attacks aimed at clearing virus infected cells from the liver [ 57 ].…”

Harnessing adipose‑derived stem cells to release specialized secretome for the treatment of hepatitis B

“…cMcdJ-AP-2016-001). The in vivo model of chronic hepatitis B was generated by an intravenous injection of pcdNA-HBx (4 µg pcdNA-HBx and in vivo-jetPEI ® Transfection mix, once a week for 6 weeks) into the mice, as previously described (21,22). Subsequently, the experimental mice received 4 intravenous injections (twice a week for 2 weeks through the tail vein) of secretome (100 µl for each injection).…”