Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2024; 30(14): 2038-2058
Published online Apr 14, 2024. doi: 10.3748/wjg.v30.i14.2038
Comparative transcriptomic analysis reveals the molecular changes of acute pancreatitis in experimental models
Pan Zheng, Xue-Yang Li, Xiao-Yu Yang, Huan Wang, Ling Ding, Cong He, Jian-Hua Wan, Hua-Jing Ke, Nong-Hua Lu, Nian-Shuang Li, Yin Zhu
Pan Zheng, Xue-Yang Li, Xiao-Yu Yang, Huan Wang, Ling Ding, Cong He, Jian-Hua Wan, Hua-Jing Ke, Nong-Hua Lu, Nian-Shuang Li, Yin Zhu, Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
Co-corresponding authors: Yin Zhu and Nian-Shuang Li.
Author contributions: Zhu Y and Li NS designed and coordinated the study; Zheng P and Li XY completed the experimental testing and wrote the article; Wan JH and Yang XY were in charge of animal modeling; He C and Ke HJ were responsible for data download and analysis in GEO database; Ding L and Wang H bred transgenic mouse; Zhu Y, Lu NH and Li NS revised and verified the article; all authors were involved in the critical review of the results and have contributed to, read, and approved the final manuscript. The reason for choosing Zhu Y and Li NH as co-corresponding authors is that Zhu Y and Li NH have made equal efforts in the whole research process, played a common important role in the design and guidance of the paper, and ensured the quality and reliability of the paper. Pan Z and Li XY contributed equally to this article.
Supported by National Natural Science Foundation of China, No. 82260133 and No. 82370661; the Academic and Technical Leader of major disciplines in Jiangxi Province, No. 20225BCJ23021; the Jiangxi Medicine Academy of Nutrition and Health Management, No. 2022-PYXM-01; the Natural Science Foundation of Jiangxi Province, No. 20224ACB216004; and the Technological Innovation Team Cultivation Project of the First Affiliated Hospital of Nanchang University, No. YFYKCTDPY202202.
Institutional animal care and use committee statement: The First Affiliated Hospital of Nanchang University approved experimental animal welfare ethics Approved by the Experimental Animal Welfare Ethics Committee of the First Affiliated Hospital of Nanchang University, Zhu Yin, Gastroenterology Department of our Hospital, "Research on the mechanism of Bifidobacterium pseudolongum Protecting intestinal mucosal Barrier in acute pancreatitis by activating NOD2-autophagy signal axis" (Approval number: CDYFYIACUC-202306QR022), does not violate the ethical principles of experimental animal welfare, and agrees to carry out the research under the approved protocol. Experimental animal Welfare Ethics Committee of the First Affiliated Hospital of Nanchang University
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The first author obtained two files, GSE109227 and GSE194331, from the public database GEO for validation purposes.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yin Zhu, MD, PhD, Chief Doctor, Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang 330006, Jiangxi Province, China. ndyfy01977@ncu.edu.cn
Received: December 8, 2023
Peer-review started: December 8, 2023
First decision: January 4, 2024
Revised: January 19, 2024
Accepted: March 1, 2024
Article in press: March 1, 2024
Published online: April 14, 2024
Processing time: 126 Days and 14.5 Hours
ARTICLE HIGHLIGHTS
Research background

Acute pancreatitis (AP) is a severe abdominal condition with an increasing incidence rate. Currently, there are no specific therapeutic approaches targeting the underlying causes of this disease. Research on AP is still in its early stages, and this study focuses on the molecular changes associated with inflammation and apoptosis, two major pathological events in AP. The aim is to identify new potential targets for treatment interventions.

Research motivation

This study primarily focused on the molecular changes in AP, indicating significant alterations in inflammation and apoptosis. The research also identified key genes involved in the TLR and NOD signaling pathways, as well as in the apoptotic signaling pathway, highlighting new research and intervention targets for future investigations in this field.

Research objectives

The purpose of this research was to investigate the parthenogenesis and molecular changes associated with AP. In fact, we have identified genes that play important roles in the inflammatory and apoptotic signaling pathways. These findings provide directions for future studies aimed at reducing inflammation and alleviating pancreatic necrosis in AP, as well as discovering new therapeutic approaches for AP.

Research methods

In this study, RNA sequencing analysis was employed to investigate the molecular changes associated with AP and identify key genes involved. Additionally, external GSE from human peripheral blood samples and mouse pancreatic tissues were downloaded and used for validation purposes. Transgenic mice models were also utilized to further validate the findings after induction of AP.

Research results

The molecular changes in inflammation and apoptosis are consistent between different animal models of AP and transgenic AP models. The TLR and NOD signaling pathways play important roles in the inflammatory response of AP, with key genes identified as TLR1, TLR7, RIPK3, and OAS2. TUBA1A and GADD45A have been identified as crucial molecules involved in regulating acinar cell apoptosis in AP. However, further analysis is still needed to investigate AP associated with various etiologies and different modeling method.

Research conclusions

New theories: (1) TUBA1A and GADD45A are key molecules involved in regulating apoptosis of vesicular cells in AP; and (2) Transgenic mice, hM3/Ptf1a(cre) with AP induced by caerulein, exhibit similar molecular changes. New method: Transgenic mice carrying the hM3/Ptf1α(cre) construct were generated and successfully developed AP.

Research perspectives

Using the latest single-cell sequencing technology to investigate the pathogenic mechanisms of AP in-depth.