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Front Physiol. 2018 May 29;9:632. doi: 10.3389/fphys.2018.00632. eCollection 2018.

Ductal Mucus Obstruction and Reduced Fluid Secretion Are Early Defects in Chronic Pancreatitis.

Author information

1
First Department of Medicine, University of Szeged, Szeged, Hungary.
2
Department of Translational Pulmonology, Translational Lung Research Center Heidelberg, German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany.
3
MTA-SZTE Momentum Epithel Cell Signalling and Secretion Research Group, Szeged, Hungary.
4
Department of Pathophysiology, University of Szeged, Szeged, Hungary.
5
Department of Pediatric Pulmonology and Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
6
Department of Internal Medicine A, Universitätsmedizin Greifswald, Greifswald, Germany.
7
Institute of Radiology, Universitätsmedizin Greifswald, Greifswald, Germany.
8
Department of Pathology, University of Szeged, Szeged, Hungary.
9
Berlin Institute of Health, Berlin, Germany.
10
Institute for Translational Medicine, First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary.
11
MTA-SZTE Translational Gastroenterology Research Group, Szeged, Hungary.

Abstract

Objective: Defective mucus production in the pancreas may be an important factor in the initiation and progression of chronic pancreatitis (CP), therefore we aimed to (i) investigate the qualitative and quantitative changes of mucus both in human CP and in an experimental pancreatitis model and (ii) to correlate the mucus phenotype with epithelial ion transport function. Design: Utilizing human tissue samples and a murine model of cerulein induced CP we measured pancreatic ductal mucus content by morphometric analysis and the relative expression of different mucins in health and disease. Pancreatic fluid secretion in CP model was measured in vivo by magnetic resonance cholangiopancreatography (MRCP) and in vitro on cultured pancreatic ducts. Time-changes of ductal secretory function were correlated to those of the mucin production. Results: We demonstrate increased mucus content in the small pancreatic ducts in CP. Secretory mucins MUC6 and MUC5B were upregulated in human, Muc6 in mouse CP. In vivo and in vitro fluid secretion was decreased in cerulein-induced CP. Analysis of time-course changes showed that impaired ductal ion transport is paralleled by increased Muc6 expression. Conclusion: Mucus accumulation in the small ducts is a combined effect of mucus hypersecretion and epithelial fluid secretion defect, which may lead to ductal obstruction. These results suggest that imbalance of mucus homeostasis may have an important role in the early-phase development of CP, which may have novel diagnostic and therapeutic implications.

KEYWORDS:

chronic pancreatitis; ductal epithelium; epithelial fluid secretion; experimental pancreatitis; mucus

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