ACE2 mitigates PEDV-induced endoplasmic reticulum stress and autophagy by inhibiting ROS production

Abstract

Role of ACE2 in regulating inflammatory damage has been recognized, its association with ER stress and autophagy under PEDV infection remains elusive. To clarify the above associations, this study first established a stress injury model through PEDV infection to determine whether it can induce ER stress or autophagy. Then, the relationships between ER stress, autophagy and ROS under PEDV infection were verified. Finally, the immune regulatory role and molecular mechanism of ACE2 in PEDV induced ER stress and autophagy were explored by regulating the expression of ACE2. The results showed that PEDV elicited ER stress and activates the UPR response. Autophagy was triggered by PEDV to facilitate its replication with the involvement of ER stress as a mediator. ER stress and autophagy were both consequences of PEDV replication within cells. PEDV caused accumulation of ROS. ROS plays a pivotal role as an upstream regulatory factor in ER stress and autophagy. However, ACE2 plays a pivotal regulatory role in the aforementioned cellular processes. ACE2 inhibited ER stress and autophagy by reducing intracellular ROS production. These results reveal that PEDV infection can induce ER stress and mediate the occurrence of autophagy, and this process is regulated by the upstream factor ROS. Overexpression of ACE2 inhibits ER stress and autophagy by reducing the production of intracellular ROS, thereby restoring the REDOX homeostasis of host cells, and mitigating cell damage caused by PEDV. The research results provide new ideas and theoretical basis for ACE2 in intestinal inflammatory injury induced by PEDV infection.