Pancreatic Disorders & Therapy
Open Access
ISSN: 2165-7092
ISSN: 2165-7092
Masahiko Hirota
Kumamoto Regional Medical Center, Japan
Keynote: Pancreat Disord Ther
Introduction: Autophagy is an intracellular bulk degradation process within cells. We previously showed that excessive autophagy was induced in the pancreas of Psti (pancreatic secretory trypsin inhibitor)-knockout mice (Gastroenterology 129: 696.). We also confirmed that excessive autophagy is induced in the pancreas of cerulein-induced acute pancreatitis. However, the role of autophagy in acute pancreatitis (whether autophagy activates trypsinogen to trypsin within the acinar cells or autophagy is induced in response to trypsin activation to dissolve harmful trypsin) is not well elucidated. Objectives: The objectives are to elucidate the role of autophagy in acute pancreatitis. Masahiko Hirota We developed and analyzed two experimental systems: 1) Psti and Atg5 (autophagy-related gene 5) doubledeficient mice and 2) acinar cell-specific (conditional) Atg5 deficient mice. Atg5 is one of the key proteins to precede the autophagic process and Atg5 deficient mice could not induce autophagy. Results: 1) Both intraacinar trypsin activity and acinar cell destruction were not induced in Psti and Atg5 double-deficient mice. 2) Loss of autophagy caused resistance to activation of trypsinogen to trypsin within the acinar cells in conditional Atg5 deficient mice. The severity of acute pancreatitis induced by cerulein was also greatly reduced in conditional Atg5 deficient mice. These results indicate that autophagy is essential for trypsinogen activation to trypsin in the pancreatic acinar cells and exerts acinar cell destruction. Conclusion: Autophagy activates trypsinogen and triggers the development of acute pancreatitis.
Masahiko Hirota has completed his PhD from Kumamoto Unversity. He is the director of Kumamoto Regional Medical Center, Japan and the clinical professor of Department of Gastroenterological Surgery, KumamoTo University Medical School, Japan. He has published more than 250 papers in reputed journals.
E-mail: mhirota@krmc.or.jp