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

Artikel i vetenskaplig tidskrift
Författare Elisabeth E. L. Nyström
George M. H. Birchenough
Sjoerd van der Post
Liisa Arike
A. D. Gruber
Gunnar C. Hansson
Malin E V Johansson
Publicerad i Ebiomedicine
Volym 33
Sidor 134-143
ISSN 2352-3964
Publiceringsår 2018
Publicerad vid Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
Sidor 134-143
Språk en
Länkar dx.doi.org/10.1016/j.ebiom.2018.05....
Ämnesord 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
Ämneskategorier Invärtesmedicin

Sammanfattning

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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