Articles
Vol. 70 No. 2 (2026)
Colchicine alleviates severe acute pancreatitis in rats by inhibiting acinar cell ferroptosis via LCN2/MAPK/ERK signaling axis
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 11 May 2026
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Colchicine (COL) is known to ameliorate severe acute pancreatitis (SAP), yet the precise molecular mechanisms remain elusive. This study integrates bioinformatics with in vivo experimentation to elucidate the mechanism by which COL attenuates SAP. An SAP rat model was established via sodium taurocholate injection. Key therapeutic targets were screened using transcriptomics and network pharmacology. Mechanistic validation utilized AAV-mediated lipocalin-2 (LCN2) overexpression, the ferroptosis inhibitor ferrostatin-1 (Fer-1), and the ERK inhibitor PD98059. COL treatment significantly ameliorated pancreatic pathological injury, inflammatory cell infiltration, and cytokine release. LCN2 was identified as a pivotal target markedly upregulated in SAP but downregulated by COL. Crucially, LCN2 overexpression reversed COL’s therapeutic benefits and restored ferroptosis markers (COX2, Fe2+, ROS) while suppressing anti-ferroptotic indices. Notably, this reversal was effectively abrogated by co-treatment with either Fer-1 or PD98059, confirming the involvement of the MAPK/ERK pathway. This study is the first to elucidate that COL inhibits ferroptosis in pancreatic acinar cells by downregulating LCN2 and subsequently suppressing the LCN2/MAPK/ERK signaling axis. These findings provide a novel molecular basis for COL and highlight a potential target for therapeutic intervention in SAP.
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Ethics Approval
This study was approved by the Experimental Medicine Research Center of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineCRediT authorship contribution
Liu Yang, study protocol design, data collection, data analysis, literature search, writing – original drafting. Xiaoyi Zheng, Yang Zhang, Yue Li, Lei Li, Feng Liu, research management, contribution to funding acquisition and study management. All authors read and approved the final manuscript and agreed to be accountable for all aspects of the work.
Supporting Agencies
National Natural Science Foundation of China , Shanghai Science and Technology Commission FoundationData Availability Statement
Data generated or analyzed during this study are available from the corresponding author on reasonable request.
How to Cite
1.
Yang L, Zheng X, Zhang Y, Li Y, Li L, Liu F. Colchicine alleviates severe acute pancreatitis in rats by inhibiting acinar cell ferroptosis via LCN2/MAPK/ERK signaling axis. Eur J Histochem [Internet]. 2026 May 11 [cited 2026 May 12];70(2). Available from: https://www.ejh.it/ejh/article/view/4557
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