Double deficiency of cathepsin B and L in the mouse pancreas alters trypsin activity without affecting acute pancreatitis severity.
Pancreatology
; 22(7): 880-886, 2022 Nov.
Article
en En
| MEDLINE
| ID: mdl-36038449
ABSTRACT
BACKGROUND:
Premature intracellular trypsinogen activation has long been considered a key initiator of acute pancreatitis (AP). Cathepsin B (CTSB) activates trypsinogen, while cathepsin L (CTSL) inactivates trypsin(ogen), and both proteins play a role in the onset of AP.METHODS:
AP was induced by 7 hourly intraperitoneal injections of cerulein (50 µg/kg) in wild-type and pancreas-specific conditional Ctsb knockout (CtsbΔpan), Ctsl knockout (CtslΔpan), and Ctsb;Ctsl double-knockout (CtsbΔpan;CtslΔpan) mice. Pancreatic samples were collected and analyzed by histology, immunohistochemistry, real-time PCR, and immunoblots. Trypsin activity was measured in pancreatic homogenates. Peripheral blood was collected, and serum amylase activity was measured.RESULTS:
Double deletion of Ctsb and Cstl did not affect pancreatic development or mouse growth. After 7 times cerulein injections, double Ctsb and Ctsl deficiency in mouse pancreases increased trypsin activity to the same extent as that in Ctsl-deficient mice, while Ctsb deficiency decreased trypsin activity but did not affect the severity of AP. CtsbΔpan;CtslΔpan mice had comparable serum amylase activity and histopathological changes and displayed similar levels of proinflammatory cytokines, apoptosis, and autophagy activity compared with wild-type, CtsbΔpan, and CtslΔpan mice.CONCLUSION:
Double deletion of Ctsb and Ctsl in the mouse pancreas altered intrapancreatic trypsin activity but did not affect disease severity and inflammatory response after cerulein-induced AP.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Pancreatitis
/
Catepsina B
Límite:
Animals
Idioma:
En
Revista:
Pancreatology
Asunto de la revista:
ENDOCRINOLOGIA
/
GASTROENTEROLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón