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Actin-Depolymerizing Factor and Cofilin-1 Have Unique and Overlapping Functions in Regulating Intestinal Epithelial
Dongdong Wang1, Nayden G Naydenov1, Alex Feygin1
1Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia.
The American Journal of Pathology
|February 16, 2016
Summary
Actin-depolymerizing factor (ADF) and cofilin-1 regulate intestinal epithelial junctions. ADF limits inflammation severity, while both proteins are crucial for rebuilding these barriers during injury.
Area of Science:
- Cell Biology
- Gastroenterology
- Immunology
Background:
- The actin cytoskeleton is vital for intestinal mucosal barrier integrity, controlling epithelial adherens and tight junctions (AJs and TJs).
- Actin dynamics, regulated by the actin-depolymerizing factor (ADF) and cofilin family, are essential for junction assembly and function.
- Understanding these proteins' roles is key to addressing intestinal barrier dysfunction.
Purpose of the Study:
- To investigate the roles of ADF and cofilin-1 in regulating intestinal epithelial adherens and tight junctions.
- To determine how ADF and cofilin-1 impact epithelial barrier permeability and junction assembly.
- To assess the in vivo role of ADF in intestinal inflammation.
Main Methods:
- RNA interference (RNAi) was used to deplete ADF and cofilin-1 in human colonic epithelial cells.
- Paracellular permeability assays were performed using small ions and large molecules.
- Morphological analysis of AJs and TJs and the perijunctional actin belt was conducted.
- Intestinal permeability and inflammation were assessed in ADF-null mice during dextran sodium sulfate-induced colitis.
Main Results:
- Depletion of ADF or cofilin-1 increased epithelial permeability to small ions.
- Cofilin-1 depletion, but not ADF depletion, increased permeability to large molecules.
- Loss of ADF or cofilin-1 impaired de novo assembly of AJs, TJs, and the perijunctional actin belt.
- ADF-null mice showed increased intestinal permeability and heightened inflammation during colitis, despite normal baseline barrier function.
Conclusions:
- ADF and cofilin-1 are critical for the dynamic remodeling and assembly of intestinal epithelial junctions.
- ADF plays a significant role in limiting the severity of intestinal inflammation and maintaining barrier function during injury.
- These findings highlight ADF and cofilin-1 as potential therapeutic targets for inflammatory bowel diseases.
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