Circular RNA CircEZH 2 Suppresses Transmissible Gastroenteritis Coronavirus induced Opening of Mitochondrial Permeability Transition Pore via Targeting MiR 22 in IPEC J 2
Transmissible gastroenteritis (TGE) is a contagious and infectious disease that is characterized by severe vomiting and diarrhea of swine especially piglet, and caused by transmissible gastroenteritis coronavirus (TGEV) TGEV infection provokes mitochondrial damage of porcine intestinal epthelial cell (IPEC) which is responsible for inflammation and cell death. In our previous study, we have demonstrated that circular RNA circEZH2 was down regulated during TGEV infection and promoted the activation of nuclear factor kappa light chain enhancer of activated B cells (NF kB) via targeting miR 22 in porcine intestinal epithelial cell line (IPEC J2) Activation of NF kB is an important factor for mitochondrial damage. Mitochondrial permeability transition pore (mPTP) opening is a key reason for mitochondrial damage. So, we speculate that circEZH2 may regulate TGEV induced mPTP opening via NF kB pathway. In the present study, we found that mPTP opening of IPEC J2 was occured during TGEV infection and suppressed by circEZH2 via attaching miR 22. Hexokinase 2 (HK2) and interleukin 6 (IL 6) were identified as the targets of miR 22. Silencing HK2 enhanced TGEV induced mPTP opening, while no effect on NF kB pathway. Silencing IL 6 promoted TGEV induced mPTP opening and inhibited NF kB pathway. Inhibitor of NF kB increased TGEV induced mPTP opening. The data revealed that TGEV induced mPTP opening was regulated via two pathways: circEZH2/miR 22/HK2 axis and circEZH2/miR 22/IL 6/NF kB axis.