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

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.