Endoplasmic reticulum stress promotes caspase-1-dependent acinar cell pyroptosis through the PERK pathway to aggravate acute pancreatitis

This is the authors' abstract. We don't add key points for this paper.

The purpose of this study was to explore whether and how endoplasmic reticulum stress (ERS) could promote caspase-1-dependent pancreatic acinar cell pyroptosis via the protein kinase R-like ER kinase (PERK) pathway to aggravate acute pancreatitis (AP). Wistar rats and AR42J cells were used to establish the AP model. When indicated, ERS regulation was performed prior to AP induction,and genetic regulation was performed prior to ERS induction. First, we found that caspase-1-dependent pyroptosis and pyroptotic injury were regulated by ERS in AP. By regulating three pathways in the UPR, ERS promotes caspase-1-dependent pyroptosis and pyroptotic injury through the PERK pathway. To further validate that ERS promotes caspase-1-dependent pyroptosis and pyroptotic injury through PERK, we used the PERK inhibitor ISRIB. In conclusion, our results indicated that ERS exacerbates AP by promoting caspase-1-dependent pyroptosis via the PERK pathway.