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.