Pancreas transcription factor 1alpha expression is regulated in pancreatitis.

BACKGROUND: Expression of acinar cell-specific genes requires the pancreas transcription factor 1alpha (Ptf1alpha). p48 is the only component of Ptf1alpha that is involved in both acinar gene regulation and pancreatic ontogenesis.
MATERIALS AND METHODS: To determine whether Ptf1alpha/p48 expression is regulated during pancreatitis, acute pancreatitis was induced in rats by repeated caerulein injections; early chronic pancreatitis by the combined administration of caerulein and cyclosporin A; and focal pancreas fibrosis by trinitrobenzene sulfonic acid infusion into the pancreatic duct. AR42J cells were used to examine caerulein effects on acinar cells. Ptf1alpha/p48 expression was examined using immunohistochemistry, Western blotting, and qRT-PCR methods.
RESULTS: In acute pancreatitis, Ptf1alpha/p48 decreased markedly within 6 h as determined by Western blotting and immunohistochemistry. After 24 h, Ptf1alpha/p48 increased continuously and normalized at day six. In contrast, pancreas amylase reached a nadir at 48 h, when Ptf1alpha/p48 had largely recovered. In the early chronic pancreatitis model Ptf1alpha/p48 levels did not completely recover even at day 14, and this was associated with a failure to restore normal histology and amylase content. qRT-PCR showed that p48 mRNA were reduced after pancreatitis induction and were followed by a decrease in elastase mRNA. In the focal pancreas fibrosis model, Ptf1alpha/p48 expression was undetectable in areas with substantial acinar cell loss and tubular complexes. Caerulein did not affect Ptf1alpha/p48 expression in AR42J cells.
CONCLUSIONS: Ptf1alpha/p48 protein and mRNA levels are regulated in acute and chronic experimental pancreatitis. Inability to re-express Ptf1alpha/p48 after injury may preclude acinar cell differentiation and appropriate pancreatic regeneration.