研究発表を行った学会；第２６回日本分子生物学会年会
２００３年１２月１０日〜１３日（神戸）
タイトル；Lack of pancreatic secretory trypsin inhibitor induces autophagic cell death of pancreatic acinar cells.
発表者；大村谷　昌樹　氏
　　　（熊本大学　発生医学研究センター　臓器形成分野）
Abstract；
Point mutations in the human pancreatic secretory trypsin inhibitor (PSTI) gene which is thought to inhibit intracellular activation of trypsin are associated with hereditary pancreatitis. In addition, PSTI has a similar structure to epidermal growth factor (EGF). To examine the function of PSTI, we generated PSTI-deficient mice. In Psti-/- mice, autophagic degeneration of acinar cells became apparent at 16.5 days postcoitum (dpc) and the following extensive autophagic cell death resulted in death around 10 days postpartum (dpp). Although the duct-like cells in the tubular complexes strongly expressed pancreatic duodenal homeodomain containing protein 1 (Pdx1), these cells did not exhibit mitotic activity. Thus, the progressive disappearance of acinar cells in Psti-/- mice can be explained by autophagic cell death of acinar cells and impaired differentiation of stem cells into acinar cells after cell death. Our results suggest that a loss of PSTI activity could directly trigger intraacinar activation of trypsinogen, leading to autophagic cell death of pancreatic acinar cells.