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Fibrin(ogen) Is Constitutively Expressed by Differentiated Intestinal Epithelial Cells and Mediates Wound Healing
Amira Seltana1, Gabriel Cloutier1, Vilcy Reyes Nicolas1
1Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
Frontiers in Immunology
|July 11, 2022
Summary
Fibrinogen, normally removed after injury, actively promotes intestinal epithelial healing and repair in both normal and diseased states. This study challenges the idea that fibrinogen removal is always necessary for tissue repair.
Area of Science:
- Gastroenterology
- Cell Biology
- Biochemistry
Background:
- Fibrinogen (a blood protein) is typically removed after injury to allow tissue repair.
- Its role in intestinal inflammation and repair is considered context-dependent.
- The intestine constantly renews its epithelial lining, requiring efficient repair mechanisms.
Purpose of the Study:
- To investigate the role of fibrinogen in intestinal epithelial healing.
- To challenge the conventional view that fibrinogen must be removed for tissue repair.
- To explore fibrinogen's contribution to both physiological and pathological intestinal repair.
Main Methods:
- Immunofluorescence and immunoelectron microscopy to visualize fibrinogen.
- Quantitative PCR to assess gene expression.
- Wound healing assays on epithelial cell monolayers and co-cultures.
- In vivo studies using mice treated with dabigatran and dextran sulfate sodium.
Main Results:
- Fibrinogen is constitutively produced by intestinal epithelial cells and deposited in the basement membrane.
- Fibrinogen accelerates epithelial wound closure in a PI3K-dependent manner.
- Increased fibrinogen accumulation was observed in Crohn's disease tissues.
- Inhibition of fibrin formation worsened dextran sulfate sodium-induced colitis in mice.
Conclusions:
- Fibrinogen acts as a substrate for intestinal epithelial wound healing under physiological and pathological conditions.
- Fibrinogen actively contributes to epithelial repair, contrary to the notion of its mandatory removal.
- Fibrinogen plays a crucial role in maintaining intestinal integrity and healing, particularly in inflammatory conditions.
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