期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 34, 页码 12396-12401出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1407597111
关键词
protease; von Willebrand factor; gastrointestinal tract
资金
- Swedish Research Council
- Swedish Cancer Society
- Knut and Alice Wallenberg Foundation
- Inga Britt and Arne Lundberg Foundation
- Sahlgren's University Hospital
- Wilhelm and Martina Lundgren's Foundation
- Torsten och Ragnar Soderbergs Stiftelser
- Sahlgrenska Academy
- National Institute of Allergy and Infectious Diseases [U01AI095473]
- Swedish Foundation for Strategic Research-Mucus, Bacteria and Colitis SSF Center (MBC) of the Innate Immunity Program
- Deutsche Forschungsgemeinschaft (DFG) Collaborative Research Center [CRC877]
The mucus that covers and protects the epithelium of the intestine is built around its major structural component, the gel-forming MUC2 mucin. The gel-forming mucins have traditionally been assumed to be secreted as nonattached. The colon has a two-layered mucus system where the inner mucus is attached to the epithelium, whereas the small intestine normally has a nonattached mucus. However, the mucus of the small intestine of meprin beta-deficient mice was now found to be attached. Meprin beta is an endogenous zinc-dependent metalloprotease now shown to cleave the N-terminal region of the MUC2 mucin at two specific sites. When recombinant meprin beta was added to the attached mucus of meprin beta-deficient mice, the mucus was detached from the epithelium. Similar to meprin beta-deficient mice, germ-free mice have attached mucus as they did not shed the membrane-anchored meprin beta into the luminal mucus. The ileal mucus of cystic fibrosis (CF) mice with a nonfunctional cystic fibrosis transmembrane conductance regulator (CFTR) channel was recently shown to be attached to the epithelium. Addition of recombinant meprin beta to CF mucus did not release the mucus, but further addition of bicarbonate rendered the CF mucus normal, suggesting that MUC2 unfolding exposed the meprin beta cleavage sites. Mucus is thus secreted attached to the goblet cells and requires an enzyme, meprin beta in the small intestine, to be detached and released into the intestinal lumen. This process regulates mucus properties, can be triggered by bacterial contact, and is nonfunctional in CF due to poor mucin unfolding.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据