Fibroblast growth factor 21 responds to taurocholic acid sodium-induced acute pancreatic injury

Ling Zhang; Yujie Lin; Xiangli Ma; Xu Fu; Peiwu Li

doi:10.1016/j.compbiomed.2025.110761

Fibroblast growth factor 21 responds to taurocholic acid sodium-induced acute pancreatic injury

Comput Biol Med. 2025 Jul 11;196(Pt A):110761. doi: 10.1016/j.compbiomed.2025.110761. Online ahead of print.

Authors

Ling Zhang¹, Yujie Lin¹, Xiangli Ma¹, Xu Fu², Peiwu Li³

Affiliations

¹ Emergency Center of the Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China.
² Emergency Medical Key Laboratory of the Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China; Cuiying Biomedical Research Center of the Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China.
³ Emergency Center of the Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China; Emergency Medical Key Laboratory of the Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China. Electronic address: lipeiw@lzu.edu.cn.

PMID: 40651202
DOI: 10.1016/j.compbiomed.2025.110761

Abstract

Acute pancreatitis (AP) represents an inflammatory condition initiated by acinar cell injury, leading to pancreatic tissue autodigestion through premature zymogen activation. However, there is currently still a lack of effective treatments capable of reversing AP. Therefore, we aimed to explore the underlying mechanisms and potential therapeutic targets of AP. Through bioinformatics analysis, 298 DEGs were identified from the pancreatic transcriptome data of mice with AP, among which fibroblast growth factor 21 (Fgf21) and autophagy-related genes were upregulated, and Fgf21 was enriched in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the results of molecular docking and dynamics simulation revealed that the recombinant FGF21 (rFGF21) interacted with PI3K regulatory subunit alpha (PIK3R1). In vivo experiments indicated that FGF21 was upregulated in the early stage of AP, potentially inhibiting the PI3K/AKT/mTOR axis, which was further inhibited by the intervention of rFGF21 and led to a significantly increased autophagic flux and alleviated pancreatic damage.

Keywords: Acute pancreatitis; Autophagic flux; Fibroblast growth factor 21; PI3K/AKT/mTOR axis; Taurocholic acid sodium.