PIAS1 upregulation confers protection against Cerulein-induced acute pancreatitis via FTO downregulation by enhancing sumoylation of Foxa2.

This research discussed the specific mechanism by which PIAS1 affects acute pancreatitis (AP). PIAS1, Foxa2, and FTO expression was assessed in Cerulein-induced AR42J cells and mice. Loss- and gain-of-function assays and Cerulein induction were conducted in AR42J cells and mice for analysis. The relationship among PIAS1, Foxa2, and FTO was tested. Cell experiments run in triplicate, and eight mice for each animal group. Cerulein-induced AP cells and mice had low PIAS1 and Foxa2 and high FTO. Cerulein induced pancreatic injury in mice and inflammation and oxidative stress in pancreatic tissues, which could be reversed by PIAS1 or Foxa2 upregulation or FTO downregulation. PIAS1 elevated SUMO modification of Foxa2 to repress FTO transcription. FTO upregulation neutralized the ameliorative effects of PIAS1 or Foxa2 upregulation on Cerulein-induced AR42J cell injury, inflammation, and oxidative stress. PIAS1 upregulation diminished FTO transcription by increasing Foxa2 SUMO modification, thereby ameliorating Cerulein-induced AP. • Cerulein-induced mice and cells have low PIAS1 and Foxa2 but high FTO expression. • PIAS1 or Foxa2 upregulation or FTO downregulation relieves AP progression in mice. • PIAS1 mediates sumoylation of Foxa2 in AP cells. • Foxa2 curbs FTO transcription to mitigate Cerulein-induced cell injury. • PIAS1 upregulation ameliorates Cerulein-induced cell injury via Foxa2/FTO axis. [ABSTRACT FROM AUTHOR]