期刊
GASTROENTEROLOGY
卷 155, 期 4, 页码 1017-1021出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2018.06.041
关键词
Mouse Model; Pancreas; Inflammation; Proteolysis
资金
- National Institutes of Health [R01 DK082412, R01 DK058088]
- National Pancreas Foundation
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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