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Chymotrypsin Reduces the Severity of Secretagogue-Induced Pancreatitis in Mice

Zsanett Jancsó1, Eszter Hegyi1, Miklós Sahin-Tóth1

  • 1Center for Exocrine Disorders, Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, Massachusetts.

Gastroenterology
|August 5, 2018
PubMed

Insights

Chymotrypsinogen B1 (CTRB1) deficiency exacerbates pancreatitis by increasing trypsin activity. CTRB1 protects against pancreatitis by controlling trypsin levels, suggesting targeted therapies.

Area of Science:

  • Biochemistry
  • Gastroenterology
  • Genetics

Background:

  • Intrapancreatic activation of proteases like trypsin and chymotrypsin is crucial in pancreatitis development.
  • Human genetics suggest chymotrypsin regulates trypsin activity, but animal models lack this evidence.

Purpose of the Study:

  • To investigate the role of chymotrypsinogen B1 (CTRB1) in pancreatitis using a mouse model.
  • To determine if CTRB1 deficiency affects intrapancreatic trypsin activity and pancreatitis severity.

Main Methods:

  • CRISPR-Cas9 gene editing was used to create CTRB1-deficient mice.
  • Pancreatitis was induced in CTRB1-deficient and control mice using cerulein administration.

Main Results:

  • CTRB1-deficient mice exhibited significantly higher intrapancreatic trypsin activity after cerulein administration.
  • These mice also developed more severe pancreatitis compared to control mice.
  • CTRB1 deficiency leads to increased trypsin activity and pancreatitis severity.

Conclusions:

  • CTRB1 plays a protective role against secretagogue-induced pancreatitis by limiting intrapancreatic trypsin activity.
  • Future pancreatitis treatments using protease inhibitors should target trypsin, not chymotrypsin.
Keywords:
InflammationMouse ModelPancreasProteolysis

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