hsp72 overexpression accelerates the recovery from caerulein-induced pancreatitis从caerulein-induced胰腺炎hsp72过度加速经济复苏.pdfVIP

Hsp72 Overexpression Accelerates the Recovery from Caerulein-Induced Pancreatitis 1 1 1 1 2 Mariia Lunova *, Eugen Zizer , Ozlem Kucukoglu , Carolin Schwarz , Wolfgang H. Dillmann , 1 1 Martin Wagner , Pavel Strnad * 1 Department of Internal Medicine I, University Medical Center Ulm, Ulm, Germany, 2 Department of Medicine, Division of Endocrinology and Metabolism, University of California San Diego, San Diego, California, United States of America Abstract Background and Aims: Heat shock protein (Hsp) 72 is a molecular chaperone which is upregulated in response to a variety of stress situations and has a general cytoprotective function. Increased Hsp72 levels were implicated in protection from acute pancreatitis; a hypothesis which was not tested in a transgenic mouse model yet. Methods: To analyze the role of Hsp72 during acute pancreatitis, well-characterized transgenic animals overexpressing rat Hsp72 (Hsp72 mice) under the control of the ß-actin promoter were subjected to caerulein- and L-arginine-induced acute pancreatitis. The severity of experimental pancreatitis was determined via serum lipase levels, morphometric evaluation and quantification of pancreatic edema/inflammation. Results: Hsp72 mice displayed ,100-times Hsp72 overexpression, but no changes in the remaining chaperones. Robust Hsp72 signal was observed in pancreatic acini, but not in islets or ductal cells. In both models, elevated Hsp72 did not protect from development of acute pancreatitis and the pancreatitis-associated lung injury, but accelerated recovery from caerulein-induced tissue injury (lower lipase levels, edema, inflammation and necrosis 36 h after caerulein administration). The observed prote