Galectin-2 and -4, but not galectin-1, promote intestinal epithelial wound healing in vitro through a TGF-beta-independent mechanism

Inflamm Bowel Dis. 2008 Oct;14(10):1366-72. doi: 10.1002/ibd.20499.


Background: Inflammatory bowel diseases (IBDs) are characterized by various degrees of mucosal surface damage and subsequent impairment of the intestinal barrier function. Resealing of the epithelial barrier requires intestinal cell migration and proliferation. Galectins are increasingly recognized as novel regulators of inflammation. Thus, we aimed to explore the effect of galectin-2 (Gal-2) and Gal-4 on epithelial cell function and wound healing.

Methods: Binding of Gal-2 and Gal-4 was determined by flow cytometric analysis and binding sites by SDS-PAGE electrophoresis. Cell migration by Gal-1, -2, and -4 was determined by a wound-healing assay. Cell cycle analysis and detection of apoptosis were determined by flow cytometric analysis.

Results: Gal-2 and Gal-4 bind to epithelial cells at the E-cadherin/beta-catenin complex. Both galectins significantly enhanced intestinal epithelial cell restitution in vitro. This enhancement of epithelial cell restitution was TGF-beta-independent. In contrast, Gal-1 decreased epithelial cell migration TGF-beta dependently. By performing cell cycle analysis, we show that Gal-2 and Gal-4 increased cyclin B1 expression and consequently cell cycle progression, while Gal-1 inhibited cell cycling. Determining the influence of Gal-2 and Gal-4 on epithelial cell apoptosis, we showed no induction of apoptosis, whereas Gal-1 significantly induced apoptosis of epithelial cells caspase-independently.

Conclusions: Gal-2 and Gal-4 bind to intestinal epithelial cells and promote their restitution. Thus, our study provides for the first time evidence that these galectins play a significant role in intestinal wound-healing processes and might exert beneficial effects in diseases characterized by epithelial barrier disruption like IBDs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Caco-2 Cells
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Flow Cytometry
  • Galectin 1 / therapeutic use
  • Galectin 2 / therapeutic use*
  • Galectin 4 / therapeutic use*
  • Humans
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / pathology
  • Intestinal Mucosa / injuries*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Rats
  • Transforming Growth Factor beta / physiology*
  • Wound Healing / drug effects*
  • Wound Healing / physiology
  • Wounds and Injuries / drug therapy*
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / pathology


  • Galectin 1
  • Galectin 2
  • Galectin 4
  • Transforming Growth Factor beta