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Calcium-activated Chloride Channel Regulator 1 (CLCA1) Controls Mucus Expansion in Colon by Proteolytic Activity

Journal article
Authors Elisabeth E. L. Nyström
George M. H. Birchenough
Sjoerd van der Post
Liisa Arike
A. D. Gruber
Gunnar C. Hansson
Malin E V Johansson
Published in Ebiomedicine
Volume 33
Pages 134-143
ISSN 2352-3964
Publication year 2018
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 134-143
Language en
Keywords mClca3, Gob-5, Asthma, COPD, Colon, MUC2, functional cftr channel, cystic-fibrosis, intestinal mucus, airway, disease, goblet cells, protein, mucin, mclca3, family, identification, General & Internal Medicine, Research & Experimental Medicine, ates of america, v113, p13833, ates of america, v108, p4659, ates of america, v105, p15064
Subject categories Internal medicine


Many epithelial surfaces of the body are covered with protective mucus, and disrupted mucus homeostasis is coupled to diseases such as ulcerative colitis, helminth infection, cystic fibrosis, and chronic obstructive lung disease. However, little is known how a balanced mucus system is maintained. By investigating the involvement of proteases in colonic mucus dynamics we identified metalloprotease activity to be a key contributor to mucus expansion. The effect was mediated by calcium-activated chloride channel regulator 1 (CLCA1) as application of recombinant CLCA1 on intestinal mucus in freshly dissected tissue resulted in increased mucus thickness independently of ion and mucus secretion, but dependent on its metallohydrolase activity. Further, CLCA1 modulated mucus dynamics in both human and mouse, and knock-out of CLCA1 in mice was compensated for by cysteine proteases. Our results suggest that CLCA1 is involved in intestinal mucus homeostasis by facilitating processing and removal of mucus to prevent stagnation. In light of our findings, we suggest future studies to investigate if upregulation of CLCA1 in diseases associated with mucus accumulation could facilitate removal of mucus in an attempt to maintain homeostasis. (C) 2018 The Authors. Published by Elsevier B.V.

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