Role and mechanism of mitochondrial calcium uniporter in the cytoskeleton of pancreatic ductal epithelial cells in a mouse model of acute pancreatitis

Qiaofeng CHEN; Qingzi FU; Huiying YANG; Junbo HONG; Liang ZHU; Zhenzhen YANG; Guodu TANG; Shiyu ZHANG

doi:10.12449/JCH260220

Volume 42 Issue 2

Feb. 2026

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Article Navigation > Journal of Clinical Hepatology > 2026 > 42(2): 400-408

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Role and mechanism of mitochondrial calcium uniporter in the cytoskeleton of pancreatic ductal epithelial cells in a mouse model of acute pancreatitis

DOI: 10.12449/JCH260220

Qiaofeng CHEN^{1, 2, 3},
Qingzi FU⁴,
Huiying YANG⁵,
Junbo HONG^{1, 2, 3},
Liang ZHU^{1, 2, 3},
Zhenzhen YANG^{1, 2, 3},
Guodu TANG⁵,
Shiyu ZHANG^{1, 2, 3
,
,
,}

1.
Department of Gastroenterology，The First Affiliated Hospital of Nanchang University，Nanchang 330006，China
2.
Jiangxi Provincial Key Laboratory of Digestive Diseases，Nanchang 330006，China
3.
Jiangxi Clinical Research Center for Gastroenterology，Nanchang 330006，China
4.
Department of Medical Genetics，Jiangxi Maternal and Child Health Hospital，Nanchang 330006，China
5.
Department of Gastroenterology，The First Affiliated Hospital of Guangxi Medical University，Nanning 530000，China

Research funding:

National Natural Science Foundation of China (82460134);

National Natural Science Foundation of China (81970558);

Natural Science Foundation of Jiangxi Province (20232BAB206021)

More Information

Corresponding author: ZHANG Shiyu， ndyfy09676@ncu.edu.cn （ORCID： 0000-0002-3596-7807）
Received Date: 2025-08-19
Accepted Date: 2025-11-13
Published Date: 2026-02-25

Abstract

Abstract

Objective To investigate the effect of mitochondrial calcium uniporter （MCU） on the cytoskeleton of pancreatic ductal epithelial cells in a mouse model of acute pancreatitis （AP） induced by caerulein （CAE）， to analyze the role of MCU in the development of AP， and to provide a theoretical basis for clinical treatment. Methods In the in vivo experiment， wild-type male C57BL6/J mice， aged 4 weeks， were randomly divided into control group and AP group， with 6 mice in each group. The mice in the AP group were given intraperitoneal injection of CAE to establish a model of AP， and those in the control group were given intraperitoneal injection of an equal volume of normal saline. Serum and pancreatic tissue samples were collected after 24 hours of modeling. HE staining was used to observe pancreatic histopathological changes； Western Blot was used to measure the expression levels of MCU， glutathione peroxidase 4 （GPX4）， and acyl-CoA synthetase long chain family member 4 （ASCL4）； kits were used to measure the serum level of amylase. In the in vitro experiment， the human pancreatic ductal epithelial cell line HPDE6-C7 was co-cultured with CAE for 24 hours to establish an in vitro AP model， and the cells were divided into control group， CAE group， RR （an MCU activity inhibitor） group， CAE+RR group， Fer-1 （an ferroptosis inhibitor） group， CAE+Fer-1 group， Erastin （an ferroptosis inducer） group， and CAE+Erastin group. CCK-8 assay was used to observe the influence of different agents on cell viability； Western Blot was used to measure the expression levels of MCU， GPX4， and ASCL4； immunofluorescence assay was used to measure reactive oxygen species （ROS）， actin cytoskeleton， and monolayer permeability； kits were used to measure the concentrations of malondialdehyde （MDA）， glutathione （GSH）， Fe²⁺， and total iron. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for comparison between two groups. Results In the in vivo experiment， compared with the control group， the AP group had significant increases in pancreatic histopathological score， the serum level of amylase， and the expression levels of MCU and ASCL4， as well as a significant reduction in the expression of GPX4 （all P<0.05）. In the in vitro experiment， compared with the control group， the CAE group had significant increases in the expression levels of MCU and ASCL4， a significant reduction in the expression of GPX4， and significant increases in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability， as well as a significant reduction in the concentration of GSH （all P<0.05）， with the presence of actin cytoskeleton disruption. Compared with the CAE group， the CAE+RR group had a significant increase in the expression level of GPX4， a significant reduction in the expression level of ASCL4， and significant reductions in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant increase in the concentration of GSH （all P<0.05）， with alleviation of actin cytoskeleton disruption. Compared with the CAE group， the CAE+Fer-1 group had significant reductions in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant increase in the concentration of GSH （all P<0.05）， with alleviation of actin cytoskeleton disruption. Compared with the CAE group， the CAE+Erastin group had significant increases in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant reduction in the concentration of GSH （all P<0.05）， with aggravation of actin cytoskeleton disruption. Conclusion During the onset of AP， MCU mediates oxidative stress-induced ferroptosis and leads to the disruption of the pancreatic ductal epithelial barrier， which may be one of the possible pathogeneses of AP.
- Pancreatitis,
- Cytoskeleton,
- Models， Animal

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References(33)

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Role and mechanism of mitochondrial calcium uniporter in the cytoskeleton of pancreatic ductal epithelial cells in a mouse model of acute pancreatitis

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Role and mechanism of mitochondrial calcium uniporter in the cytoskeleton of pancreatic ductal epithelial cells in a mouse model of acute pancreatitis

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