Increased expression of hypoxia-inducible factor-1 alpha, p48, and the notch signaling cascade during acute pancreatitis in mice

Acute pancreatitis (AP) is a complex disease that may be linked to acinar cell apoptosis and inadequate acinar cell replacement. Differentiation of acinar cells is regulated by p48, a DNA binding subunit of the transcription factor PTF1, and the Notch signaling pathway. Acinar cell apoptosis is triggered by oxygen deprivation, ie, hypoxia, by activation of hypoxia inducible factor-1alpha (HIF-1alpha). The aim of this study was to characterize by Northern blot analyses expression of HIF-1alpha, HIF-1alpha-inducible genes (GLUT-1, VEGF, p53), p48, and genes involved in the Notch signaling pathway (Notch-1, Dll1, RBPJk, HES-1) during cerulein-induced AP in mice. Maximal expression of HIF-1alpha, HIF-1alpha- inducible genes, p48, and Notch signaling genes occurred 8-12 hours after induction of AP. Maximal expression of p53 occurred 12-48 hours after induction of AP. These findings demonstrate that multiple pancreatic genes are activated acutely during AP that support pancreatic cell replenishment, regulation of expression of acinar cell-specific genes, and apoptosis.