Wound healing of intestinal epithelial cells

Abstract

The intestinal epithelial cells (IECs) form a selective permeability barrier separating luminal content from underlying tissues. Upon injury, the intestinal epithelium undergoes a wound healing process. Intestinal wound healing is dependent on the balance of three cellular events; restitution, proliferation, and differentiation of epithelial cells adjacent to the wounded area. Previous studies have shown that various regulatory peptides, including growth factors and cytokines, modulate intestinal epithelial wound healing. Recent studies have revealed that novel factors, which include toll-like receptors (TLRs), regulatory peptides, particular dietary factors, and some gastroprotective agents, also modulate intestinal epithelial wound repair. Among these factors, the activation of TLRs by commensal bacteria is suggested to play an essential role in the maintenance of gut homeostasis. Recent studies suggest that mutations and dysregulation of TLRs could be major contributing factors in the predisposition and perpetuation of inflammatory bowel disease. Additionally, studies have shown that specific signaling pathways are involved in IEC wound repair. In this review, we summarize the function of IECs, the process of intestinal epithelial wound healing, and the functions and mechanisms of the various factors that contribute to gut homeostasis and intestinal epithelial wound healing.

Keywords: Growth factors; Intestinal epithelial cell; Restitution; Toll-like receptor; Wound healing.

Figure 1

Wounded rat intestinal epithelial cell-6 cells. A: Confluent monolayers of intestinal epithelial cell (IEC)-6 cells were wounded with a razor blade. Wounded IEC-6 cells 24 h after wound formation. Wound line is shown with an arrow; B: IEC-6 cells wounded by mechanical cell denudation (× 40). Wounded cells at 0, 24 and 72 h after wound formation are shown; C: Wound margin of IEC-6 cells (× 200).

Figure 2

Various factors and signaling pathways contributing to the process of wound healing of intestinal epithelial cells and intestinal mucosa. IEC: Intestinal epithelial cell; TGF: Transforming growth factor; EGF: Epidermal growth factor; HGF: Hepatocyte growth factor; FGF: Fibroblast growth factor; KGF: Keratinocyte growth factor; IGF: Insulin-like growth factor; HB-EGF: Heparin-binding epidermal growth factor; IL: Interleukin; COX: Cyclooxygenase; TLR: Toll-like receptor; HIF: Hypoxia-inducible factor; GM-CSF: Granulocyte-macrophage colony stimulating factor; ERK: Extracellular signal-regulated kinase; MAPK: Mitogen-activated protein kinase; PI3K: Phosphatidylinositol 3-kinase; NF: Nuclear factor; STAT: Signal transducer and activator of transcription.