Pancreas transcription factor 1α expression is regulated in pancreatitis

Background Expression of acinar cell-specific genes requires the pancreas transcription factor 1 α (Ptf1 α ). p48 is the only component of Ptf1 α that is involved in both acinar gene regulation and pancreatic ontogenesis. Materials and methods To determine whether Ptf1 α /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. Ptf1 α /p48 expression was examined using immunohistochemistry, Western blotting, and qRT-PCR methods. Results In acute pancreatitis, Ptf1 α /p48 decreased markedly within 6 h as determined by Western blotting and immunohistochemistry. After 24 h, Ptf1 α /p48 increased continuously and normalized at day six. In contrast, pancreas amylase reached a nadir at 48 h, when Ptf1 α / p48 had largely recovered. In the early chronic pancreatitis model Ptf1 α /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, Ptf1 α /p48 expression was undetectable in areas with substantial acinar cell loss and tubular complexes. Caerulein did not affect Ptf1 α /p48 expression in AR42J cells. Conclusions Ptf1 α /p48 protein and mRNA levels are regulated in acute and chronic experimental pancreatitis. Inability to re-express Ptf1 α /p48 after injury may preclude acinar cell differentiation and appropriate pancreatic regeneration.