Hepatitis B virus upregulates host expression of a-1,2-mannosidases via the PPARa pathway

Hu, Song; Jiang, Li-Bin; Zou, Xiao-Jing; Yi, Wei; Tian, De-Ying

As the downregulation of MAN1C1 expression can be reversed by activation of the PPAR signaling pathway [14] , we investigated whether the HBVinduced increase in α-1,2-mannosidase expression is associated with the PPAR signaling pathway. As HepG2 cells only express PPARα and PPARγ [18] , MK886 (PPARα) and GW9662 (PPARγ) inhibitors were used to explore the effects of HBV on α-1,2-mannosidase expression after the PPARα and PPARγ pathways were blocked. The results showed that after the application of the PPARα inhibitor MK886, the effects of HBV on α-1,2mannosidase expression were neutralized; however, no such effects were found when a PPARγ inhibitor was applied ( Figure 4A ). In order to further confirm whether the PPAR signaling pathway plays a role in the HBV-mediated increase in α-1,2-mannosidase levels, we tested the effect of GW9662 and MK886 on the expression of α-1,2-mannosidase in AD38 cells. We found that MK886 did not affect the expression of MAN1C1 in AD38 cells without Tet, indicating that MK886 inhibited the increase in α-1,2-mannosidase levels caused by the Tet withdrawal. However, this phenomenon was not observed in the case of GW9662 ( Figure 4C ).