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

作者: Elisabeth E.L. Nyström , George M.H. Birchenough , Sjoerd van der Post , Liisa Arike , Achim D. Gruber

DOI: 10.1016/J.EBIOM.2018.05.031

关键词:

摘要: 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, chronic obstructive lung disease. However, little known how a balanced system maintained. By investigating involvement proteases in colonic dynamics we identified metalloprotease activity be key contributor expansion. The effect was mediated by calcium-activated chloride channel regulator 1 (CLCA1) application recombinant CLCA1 on intestinal freshly dissected tissue resulted increased thickness independently ion secretion, but dependent its metallohydrolase activity. Further, modulated both human mouse, knock-out mice compensated for cysteine proteases. Our results suggest that involved facilitating processing removal prevent stagnation. In light our findings, future studies investigate if upregulation associated accumulation could facilitate an attempt maintain homeostasis.

参考文章(50)
Santosh Kumar Behera, Ardhendu Bhusan Praharaj, Budheswar Dehury, Sapna Negi, Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases Glycoconjugate Journal. ,vol. 32, pp. 575- 613 ,(2015) , 10.1007/S10719-015-9606-6
Nancy A. Erickson, Elisabeth E. L. Nyström, Lars Mundhenk, Liisa Arike, Rainer Glauben, Markus M. Heimesaat, André Fischer, Stefan Bereswill, George M. H. Birchenough, Achim D. Gruber, Malin E. V. Johansson, The Goblet Cell Protein Clca1 (Alias mClca3 or Gob-5) Is Not Required for Intestinal Mucus Synthesis, Structure and Barrier Function in Naive or DSS-Challenged Mice PLOS ONE. ,vol. 10, pp. e0131991- ,(2015) , 10.1371/JOURNAL.PONE.0131991
Malin E.V. Johansson, Hedvig E. Jakobsson, Jessica Holmén-Larsson, André Schütte, Anna Ermund, Ana M. Rodríguez-Piñeiro, Liisa Arike, Catharina Wising, Frida Svensson, Fredrik Bäckhed, Gunnar C. Hansson, Normalization of Host Intestinal Mucus Layers Requires Long-Term Microbial Colonization. Cell Host & Microbe. ,vol. 18, pp. 582- 592 ,(2015) , 10.1016/J.CHOM.2015.10.007
Krzysztof Pawłowski, Matti Lepistö, Nina Meinander, Ulf Sivars, Mikael Varga, Elisabet Wieslander, Novel conserved hydrolase domain in the CLCA family of alleged calcium-activated chloride channels. Proteins. ,vol. 63, pp. 424- 439 ,(2006) , 10.1002/PROT.20887
Jenny K. Gustafsson, Sara K. Lindén, Ala H. Alwan, Bob J. Scholte, Gunnar C. Hansson, Henrik Sjövall, Carbachol-induced colonic mucus formation requires transport via NKCC1, K + channels and CFTR Pflügers Archiv: European Journal of Physiology. ,vol. 467, pp. 1403- 1415 ,(2015) , 10.1007/S00424-014-1595-Y
Malin E. V. Johansson, Jenny K. Gustafsson, Karolina E. Sjöberg, Joel Petersson, Lena Holm, Henrik Sjövall, Gunnar C. Hansson, Bacteria penetrate the inner mucus layer before inflammation in the dextran sulfate colitis model. PLOS ONE. ,vol. 5, ,(2010) , 10.1371/JOURNAL.PONE.0012238
M. E. V. Johansson, J. M. H. Larsson, G. C. Hansson, The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host–microbial interactions Proceedings of the National Academy of Sciences of the United States of America. ,vol. 108, pp. 4659- 4665 ,(2011) , 10.1073/PNAS.1006451107
Lars Mundhenk, Bjarki Johannesson, Pinelopi Anagnostopoulou, Josephine Braun, Melanie K. Bothe, Carsten Schultz, Marcus A. Mall, Achim D. Gruber, mCLCA3 Does Not Contribute to Calcium-Activated Chloride Conductance in Murine Airways American Journal of Respiratory Cell and Molecular Biology. ,vol. 47, pp. 87- 93 ,(2012) , 10.1165/RCMB.2010-0508OC
R Gandhi, RC Elble, AD Gruber, KD Schreur, H-L Ji, CM Fuller, BU Pauli, None, Molecular and Functional Characterization of a Calcium-sensitive Chloride Channel from Mouse Lung Journal of Biological Chemistry. ,vol. 273, pp. 32096- 32101 ,(1998) , 10.1074/JBC.273.48.32096