Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, 150001 Harbin, Heilongjiang, China; Key Laboratory of Hepatosplenic Surgery, Ministry of Education, No. 23 Youzheng Street, Nangang District, 150001 Harbin, Heilongjiang, China.
Medical Department, The First Affifiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, 150001 Harbin, Heilongjiang, China.
Int Immunopharmacol. 2023 Jul;120:110293. doi: 10.1016/j.intimp.2023.110293. Epub 2023 May 12.
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.
本研究旨在探讨内质网应激（ERS）是否以及如何通过蛋白激酶 R 样内质网激酶（PERK）途径促进半胱天冬酶-1 依赖性胰腺腺泡细胞焦亡，从而加重急性胰腺炎（AP）。使用 Wistar 大鼠和 AR42J 细胞建立 AP 模型。在诱导 AP 之前进行 ERS 调节，在诱导 ERS 之前进行基因调节。首先，我们发现 ERS 在 AP 中调节半胱天冬酶-1 依赖性细胞焦亡和焦亡性损伤。通过调节 UPR 中的三条通路，ERS 通过 PERK 通路促进半胱天冬酶-1 依赖性细胞焦亡和焦亡性损伤。为了进一步验证 ERS 通过 PERK 促进半胱天冬酶-1 依赖性细胞焦亡和焦亡性损伤，我们使用了 PERK 抑制剂 ISRIB。总之，我们的研究结果表明，ERS 通过 PERK 途径促进半胱天冬酶-1 依赖性细胞焦亡从而加重 AP。
