P53 Activated by ER Stress Aggravates Caerulein-Induced Acute Pancreatitis Progression by Inducing Acinar Cell Apoptosis
- PDF / 5,769,443 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 73 Downloads / 149 Views
ORIGINAL ARTICLE
P53 Activated by ER Stress Aggravates Caerulein‑Induced Acute Pancreatitis Progression by Inducing Acinar Cell Apoptosis Lei Zhou1 · Jie‑hui Tan1 · Wan‑yan Zhou2 · Jia Xu3 · Shi‑jing Ren4 · Zhen‑yu Lin1 · Xue‑mei Chen5 · Guo‑wei Zhang1 Received: 25 June 2019 / Accepted: 6 January 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Background and Aims Acute pancreatitis (AP) is a severe pancreatic disorder that remains associated with high mortality due to a lack of effective drugs and management strategies. This study aimed to investigate the molecular pathogenic mechanisms of AP involving p53 and endoplasmic reticulum (ER) stress pathways. Methods Expression of PRSS1 and p53 in human AP tissues was detected by immunohistochemistry and Western blotting. AP was induced with caerulein in humanized PRSS1 transgenic mice, and its severity was verified by histological imaging, evaluation of edema, serum amylase, and trypsin activity assays. A transferase-mediated d-UTP nick end-labeling assay was performed to evaluate acinar cell apoptosis associated with AP. The expression of ER stress genes was assessed by quantitative RT-PCR (qRT-PCR) and Western blotting. Results PRSS1 and p53 were highly expressed in human AP tissues. Expression of human PRSS1 in caerulein-treated mice induced significant acinar cell apoptosis and AP progression. P53 knockout significantly suppressed AP progression in humanized PRSS1 transgenic mice. The ER stress pathway was activated by PRSS1 and mediated the progression of AP in mouse pancreatic tissues. Application of a p53 inhibitor effectively ameliorated caerulein-induced AP in PRSS1 transgenic mice, while a p53 activator promoted the progression of AP. Conclusion P53, which was activated by the ER stress pathway, promoted the progression of AP in mice expressing PRSS1 by inducing acinar cell apoptosis. Keywords P53 · PRSS1 · Acute pancreatitis · ER stress · Apoptosis Lei Zhou and Jie-hui Tan have contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10620-020-06052-5) contains supplementary material, which is available to authorized users. * Guo‑wei Zhang [email protected] 1
Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou 510515, People’s Republic of China
2
Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
3
Department of Pathophysiology, Southern Medical University, Guangzhou, China
4
Department of Endocrinology, Nanfang Hospital, Southern Medical University, Guangzhou, China
5
Department of Occupational Health and Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
Introduction Acute pancreatitis (AP) is an inflammatory disorder of the pancreas that is considered an abdominal eme
Data Loading...
