Background: Expression of acinar cell-specific genes requires the pancreas transcription factor 1α (Ptf1α). p48 is the only component of Ptf1α that is involved in both acinar gene regulation and pancreatic ontogenesis. Materials and methods: To determine whether Ptf1α/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. Ptf1α/p48 expression was examined using immunohistochemistry, Western blotting, and qRT-PCR methods. Results: In acute pancreatitis, Ptf1α/p48 decreased markedly within 6 h as determined by Western blotting and immunohistochemistry. After 24 h, Ptf1α/p48 increased continuously and normalized at day six. In contrast, pancreas amylase reached a nadir at 48 h, when Ptf1α/p48 had largely recovered. In the early chronic pancreatitis model Ptf1α/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, Ptf1α/p48 expression was undetectable in areas with substantial acinar cell loss and tubular complexes. Caerulein did not affect Ptf1α/p48 expression in AR42J cells. Conclusions: Ptf1α/p48 protein and mRNA levels are regulated in acute and chronic experimental pancreatitis. Inability to re-express Ptf1α/p48 after injury may preclude acinar cell differentiation and appropriate pancreatic regeneration. © 2007 The Authors.
- Chronic pancreatitis
- Pancreatic regeneration
- Transcription factor
Molero, X., Adell, T., Skoudy, A., Padilla, M. A., Gómez, J. A., Chalaux, E., Malagelada, J. R., & Real, F. X. (2007). Pancreas transcription factor 1α expression is regulated in pancreatitis. European Journal of Clinical Investigation, 37(10), 791-801. https://doi.org/10.1111/j.1365-2362.2007.01856.x