ORIGINAL RESEARCH article
Front. Med.
Sec. Intensive Care Medicine and Anesthesiology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1566728
Pancreatic stone protein inhibits pyroptosis of pancreatic acinar cells in sepsisassociated pancreatic injury
Provisionally accepted
- Hunan Children's Hospital, Changsha, Hunan Province, China
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Sepsis-associated pancreatic injury (SPI) is characterized by an increased incidence and significantly higher mortality rates. However, its underlying pathogenesis remains inadequately understood. As an acute-phase protein secreted by the pancreas, the role of pancreatic stone protein/regenerating protein (PSP/reg) in SPI remains unclear.: A total of 137 patients were consecutively admitted to the pediatric intensive care unit (PICU) of Hunan Children's Hospital with sepsis were included. The model of sepsis-associated pancreatic injury was established through cecal ligation and puncture. Pancreatic injury was assessed using HE staining. Pyroptotic pancreatic cells were evaluated via Hoechst 33342/PI staining. The expression levels of caspase-1 in the pancreatic tissues and acinar cells were determined by immunohistochemistry and immunofluorescence. Protein levels of NLRP3, caspase-1 p20, and GSDMD-N were analyzed using Western blot. The concentrations of TNFα, IL-6, IL-1β, and IL-18 were measured by ELISA.Results and discussion: Children in dead group exhibited higher circulating PSP/reg levels compared with children in survival group. The circulating PSP/reg level in the septic shock group was significantly higher than that in the sepsis group and the severe sepsis group. The circulating PSP/reg level in the severe elevation of pancreatic amylase group was significantly higher than that in the normal pancreatic amylase group and the mild elevation of pancreatic amylase group. PSP/reg administration mitigated pancreatic tissue injury and decreased injury scores and necrosis area. The amylase activity, the serum levels of LDH, TNF-α and IL-6 were remarkably downregulated in PSP/reg-treated mice compared to the SPI mice. PSP/reg administration significantly alleviated the LPS-induced pyroptosis. Pyroptosis activation-associated proteins, NLRP3, Caspase-1 p20 and GSDMD-N in pancreatic acinar cells were greatly elevated following LPS stimulation, which decreased with PSP/reg treatment.PSP/reg may exhibit protective effects by inhibiting pancreatic pyroptosis in sepsis-associated pancreatic injury model and LPS-stimulated pancreatic acinar cells.
Keywords: Pancreatic stone protein, pyroptosis, Sepsis, Pancreatic injury, Regenerating protein
Received: 25 Jan 2025; Accepted: 21 May 2025.
Copyright: © 2025 Liu, Xiao, Lu, Zhang and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhenghui Xiao, Hunan Children's Hospital, Changsha, 410007, Hunan Province, China
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