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ACF7 regulates inflammatory colitis and intestinal wound response by orchestrating tight junction dynamics.
- Source :
-
Nature communications [Nat Commun] 2017 May 25; Vol. 8, pp. 15375. Date of Electronic Publication: 2017 May 25. - Publication Year :
- 2017
-
Abstract
- In the intestinal epithelium, the aberrant regulation of cell/cell junctions leads to intestinal barrier defects, which may promote the onset and enhance the severity of inflammatory bowel disease (IBD). However, it remains unclear how the coordinated behaviour of cytoskeletal network may contribute to cell junctional dynamics. In this report, we identified ACF7, a crosslinker of microtubules and F-actin, as an essential player in this process. Loss of ACF7 leads to aberrant microtubule organization, tight junction stabilization and impaired wound closure in vitro. With the mouse genetics approach, we show that ablation of ACF7 inhibits intestinal wound healing and greatly increases susceptibility to experimental colitis in mice. ACF7 level is also correlated with development and progression of ulcerative colitis (UC) in human patients. Together, our results reveal an important molecular mechanism whereby coordinated cytoskeletal dynamics contributes to cell adhesion regulation during intestinal wound repair and the development of IBD.
- Subjects :
- Animals
Caco-2 Cells
Cell Adhesion physiology
Colitis pathology
Colitis physiopathology
Colitis, Ulcerative etiology
Colitis, Ulcerative pathology
Colitis, Ulcerative physiopathology
Crystallography, X-Ray
Disease Models, Animal
Female
Humans
Inflammatory Bowel Diseases etiology
Inflammatory Bowel Diseases pathology
Inflammatory Bowel Diseases physiopathology
Intestinal Mucosa pathology
Intestinal Mucosa physiopathology
Male
Mice
Mice, Knockout
Microfilament Proteins chemistry
Microfilament Proteins deficiency
Microfilament Proteins genetics
Microtubules physiology
Models, Molecular
Tight Junctions pathology
Tight Junctions physiology
Wound Healing physiology
Colitis etiology
Microfilament Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 28541346
- Full Text :
- https://doi.org/10.1038/ncomms15375