Role of ZFP580 in acute pancreatitis induced by caerulein through endoplasmic reticulum stress pathway
ZI Li1,2, LIU Guanglin1,2, ZHANG Wencheng1,2, XIA Shihaii1,2, XU Wei1,2
1. Department of Gastroenterology, Characteristic Medical Center of Chinese People’s Armed Police Force, Tianjin 300162, China; 2. Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Characteristic Medical Center of Chinese People’s Armed Police Force, Tianjin 300162, China
Abstract：Objective To investigate the role of zinc finger protein 580 (ZFP580) in acute pancreatitis (AP) induced by caerulein through endoplasmic reticulum (ER) stress pathway, and provide a new therapeutic target for AP treatment.Methods MTT method was used to detect cell viability. RT-PCR and Western Blot were used to detect endoplasmic reticulum stress-related mRNA and the protein expression of ZFP580 in AP model. IRE1 inhibitor (MKC-3946) was used to observe the position of ZFP580 in endoplasmic reticulum stress related signaling pathway. After Silencing ZFP580, Hochest33342 staining and WB, RT-PCT method were used to investigate the effect of ZFP580 on the apoptosis-necrosis process.Results After using cerulein to stimulate acute pancreatitis in AR42J cells, the endoplasmic reticulum stress occurred. 8 hours later, the expression of ZFP580 started to increase (showing a time-dependent increase). After using IRE1 inhibitor (MKC-3946), the expression of ZFP580 was significantly lower than that of the group without MKC-3946 treatment (P<0.05). After silencing ZFP580, the expression of XBP-1s significantly decreased. At the same time, RT-PCR and Western blot results showed that the expression of Chop in the si-ZFP580 group was significantly higher than that in the normal AP group, while the expression of Caspase-3 was lower than that in the normal AP group. The result of Hochest staining revealed that the proportion of necrotic cells in the si-ZFP580 group was significantly higher than that in the normal AP group.Conclusions ZFP580 which may be located between IRE1 and XBP-1s may play a protective role in regulating the severity of AP by improving the apoptosis-necrosis ratio.
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2022, Vol. 33 
