AUTHOR=Balázs Anita , Balla Zsolt , Kui Balázs , Maléth József , Rakonczay Zoltán , Duerr Julia , Zhou-Suckow Zhe , Schatterny Jolanthe , Sendler Matthias , Mayerle Julia , Kühn Jens-P. , Tiszlavicz László , Mall Marcus A. , Hegyi Peter 

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

JOURNAL=Frontiers in Physiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00632

DOI=10.3389/fphys.2018.00632

ISSN=1664-042X

ABSTRACT=<p><bold>Objective:</bold> 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.</p><p><bold>Design:</bold> 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 <italic>in vivo</italic> by magnetic resonance cholangiopancreatography (MRCP) and <italic>in vitro</italic> on cultured pancreatic ducts. Time-changes of ductal secretory function were correlated to those of the mucin production.</p><p><bold>Results:</bold> We demonstrate increased mucus content in the small pancreatic ducts in CP. Secretory mucins <italic>MUC6</italic> and <italic>MUC5B</italic> were upregulated in human, <italic>Muc6</italic> in mouse CP. <italic>In vivo</italic> and <italic>in vitro</italic> fluid secretion was decreased in cerulein-induced CP. Analysis of time-course changes showed that impaired ductal ion transport is paralleled by increased <italic>Muc6</italic> expression.</p><p><bold>Conclusion:</bold> 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.</p>