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Publication : Chymotrypsin Reduces the Severity of Secretagogue-Induced Pancreatitis in Mice.

First Author  Jancsó Z Year  2018
Journal  Gastroenterology Volume  155
Issue  4 Pages  1017-1021
PubMed ID  30076839 Mgi Jnum  J:294171
Mgi Id  MGI:6455003 Doi  10.1053/j.gastro.2018.06.041
Citation  Jancso Z, et al. (2018) Chymotrypsin Reduces the Severity of Secretagogue-Induced Pancreatitis in Mice. Gastroenterology 155(4):1017-1021
abstractText  Intrapancreatic activation of the digestive proteases trypsin and chymotrypsin is an early event in the development of pancreatitis. Human genetic studies indicate that chymotrypsin controls trypsin activity via degradation, but there is no evidence of this from animal models. We used CRISPR-Cas9 to disrupt the chymotrypsinogen B1 gene (Ctrb1) in C57BL/6N mice and induced pancreatitis in CTRB1-deficient and C57BL/6N (control) mice by administration of cerulein. CTRB1-deficient mice given cerulein had significant increases in intrapancreatic trypsin activity and developed more severe pancreatitis compared with control mice. CTRB1 therefore protects against secretagogue-induced pancreatitis by reducing trypsin activity. Protease inhibitors developed for treatment of pancreatitis should be designed to target trypsin but not chymotrypsin.
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