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Annexin A1 regulates inflammatory-immune response and reduces pancreatic and extra- pancreatic injury during severe acute pancreatitis

Genes & Immunity volume 26, pages 124–136 (2025)Cite this article

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A Correction to this article was published on 29 September 2025

This article has been updated

Abstract

Severe acute pancreatitis (SAP) poses significant challenges due to its complex pathophysiology, which includes inflammatory-immune responses that cause considerable damage to both the pancreas and other tissues. In this study, we explored the role of Annexin A1 (Anxa1), a glucocorticoid-regulated protein recognized for its anti-inflammatory properties, in regulating inflammation during acute pancreatitis. Using flow cytometry, single-cell RNA sequencing, and gene expression analysis, we examined how Anxa1 expression is regulated in myeloid cells throughout acute pancreatitis, employing various animal models to evaluate the consequences of modulating Anxa1 on injuries induced by SAP. Our findings revealed dynamic regulation of Anxa1 expression in myeloid cells, with mice lacking Anxa1 exhibiting worsened pancreatic injury and heightened systemic inflammation, resulting in significant damage to extra-pancreatic organs such as the lungs, liver, and kidneys. In contrast, treatment with Ac2-26, a synthetic peptide derived from Anxa1, effectively mitigated both pancreatic and extra-pancreatic inflammation and tissue damage. Overall, this study highlights the critical role of Anxa1 in modulating inflammatory responses during acute pancreatitis. Targeting Anxa1 presents a promising therapeutic strategy to mitigate pancreatic injury and prevent systemic complications associated with severe acute pancreatitis.

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Scheme 1
Fig. 1: scRNA-seq analysis of mouse peripheral blood during AP and recovery.
Fig. 2: Anxa1 expression in the peripheral blood of human AP.
Fig. 3: ANXA1 deficiency worsens L-arginine-induced AP.
Fig. 4: ANXA1 deficiency worsens CDE-supplemented diet-induced AP.
Fig. 5: Anxa1 deficiency aggravates sodium taurocholate–induced SAP.
Fig. 6: Treatment with Ac2-26 attenuates sodium taurocholate-induced SAP.
Fig. 7: Effect of glucocorticoids on Anxa1 expression in SAP.

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Data availability

The data underlying the results presented in this study are provided within the manuscript and its supplementary materials. Furthermore, the single-cell RNA-seq data are publically accessible via the Gene Expression Omnibus (GEO) database, which may be accessed using accession number GSE249349. To access the raw data, please contact the corresponding author with a reasonable request.

Change history

  • 30 July 2025

    In the original version of Figure 3, the H&E staining image in panel E (Ac 2-26 Con group) is identical to the image in panel A (WT NaCl group). This error occurred due to an unintentional duplication during the image assembly process. We have re-examined the original experimental data and confirmed the correct H&E staining image for the Ac 2-26 Con group.In Figure 6G, the group labels 'PLA SO' and 'PLA SAP' were incorrect due to a typographical error and should be corrected to 'PBS SO' (PBS-treated sham operation group) and 'PBS SAP' (PBS-treated severe acute pancreatitis group). This mistake arose from confusion between the abbreviations 'PLA' and 'PBS' during data labeling or figure editing.

  • 29 September 2025

    A Correction to this paper has been published: https://doi.org/10.1038/s41435-025-00348-0

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Funding

This study was funded by the Excellent Young Scholars Cultivation Project of Fujian Medical University Union Hospital (2022XH025), the National Natural Science Foundation of China (No. 82103310), the Natural Science Foundation of Fujian Province (2021J01774), the Joint Funds of the Scientific and Technological Innovation Program of Fujian Province (2020Y9081), the Fujian Provincial Health Technology Project (2020GGA029), and the Youth Research Project of the Fujian Provincial Health Commission Science and Technology Project (2023QN01010127).

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Author notes

  1. These authors contributed equally: Shizhao Lin, Feihong Liang, Changgan Chen.

Authors and Affiliations

  1. Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350001, China

    Shizhao Lin

  2. Fujian Abdominal Surgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, 350001, China

    Shizhao Lin

  3. National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, 350212, China

    Shizhao Lin

  4. Department of General Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, People’s Republic of China

    Feihong Liang, Changgan Chen, Jiajing Lin, Yuwei Wu, Zelin Hou, Heguang Huang, Haizong Fang & Yu Pan

  5. Central Laboratory, Fujian Medical University Union Hospital, Fuzhou, China

    Yuwei Wu & Yu Pan

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Contributions

YP and HF conceived and designed the studies. SL, CC, YW, FL, JL, HF, ZH, and YP conducted the experiments. SL, CC, YW, and FL obtained and assessed the data. Written by YP’s hand, the first draft of the work. SL, CC, and HH worked on editing and reviewing the manuscript. Throughout its entirety, the study was supervised by YP. All authors have read and approved the article.

Corresponding authors

Correspondence to Haizong Fang or Yu Pan.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

This research involving human materials and data was conducted in accordance with the Declaration of Helsinki. The study protocol received approval from the Committee for the Ethical Review of Research at Fujian Medical University Union Hospital (Approval No. 2021KJT084). Informed consent was obtained from all participants involved in the study. The animal experiments in this study were approved by the Institutional Animal Care and Use Committee of Fujian Medical University (FJMUA2021025). All animal experiments were conducted in compliance with institutional guidelines and the ARRIVE guidelines, ensuring ethical treatment of animals and adherence to proper protocols.

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Lin, S., Liang, F., Chen, C. et al. Annexin A1 regulates inflammatory-immune response and reduces pancreatic and extra- pancreatic injury during severe acute pancreatitis. Genes Immun 26, 124–136 (2025). https://doi.org/10.1038/s41435-025-00321-x

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