Premium
Pancreas transcription factor 1α expression is regulated in pancreatitis
Author(s) -
Molero X.,
Adell T.,
Skoudy A.,
Padilla M. A.,
Gómez J. A.,
Chalaux E.,
Malagelada J. R.,
Real F. X.
Publication year - 2007
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2007.01856.x
Subject(s) - pancreatitis , acinar cell , pancreas , immunohistochemistry , medicine , amylase , blot , pancreatic disease , fibrosis , endocrinology , pathology , biology , enzyme , gene , biochemistry
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.