U.S. Department of Health and Human Services

New Insights into the Mechanism of Intestinal Lining Repair

​Researchers have discovered a new role for a protein called Wnt5a in the regeneration of damaged gut tissue. The human intestinal tract is prone to injury by conditions such as inlammatory bowel disease, where the lining of the gut is damaged as a result of chronic inlammation and irritation. An important component of the intestinal lining is a collection of specialized structures called “crypts,” which are small depressions in the lining of the gut. At the base of these crypts are intestinal stem cells, which replenish the injured lining by proliferating and maturing into speciic cell types needed to replace the damaged tissue.

Intestinal crypts are damaged during injury to the lining, but how these vital structures are replaced is unclear. A group of scientists set out to address this question using a mouse model of simulated intestinal injury by surgically removing some of the crypts in the mouse’s gut, then examining the intestinal tissue both within and nearby the damaged site. They found that cells from intact crypts near the damaged site will migrate into the wound and form a series of shallow channels, which eventually subdivide into new crypts to replace the damaged ones. When the scientists examined some of the cells in these channels, they found a high abundance of a protein called Wnt5a, which suggested that it might be important for crypt regeneration. To test this idea, the researchers looked at intestinal tissue healing in a mouse model that is missing Wnt5a from its intestinal cells. When the intestinal lining of these mice was injured, no new crypts were formed, conirming that Wnt5a was necessary for the renewal of these structures. The scientists were then interested in exactly how Wnt5a was guiding the formation of new crypts, so they looked at changes in intestinal cells in culture upon exposure to this protein. They found that the cells stopped proliferating and formed small channels, similar to what happened in the mouse model. Further analysis of the cells exposed to Wnt5a showed that this protein activates a pathway that is known to stop cell proliferation, providing insight into the mechanism by which Wnt5a supports crypt regeneration. This research sheds light on how intestinal tissue is repaired after injury, and could lead to new ways to help facilitate the regeneration of intestinal cells that are damaged in diseases like inlammatory bowel disease.

Miyoshi H, Ajima R, Luo CT, Yamaguchi TP, and Stappenbeck
TS. Wnt5a potentiates TGF-β signaling to promote colonic
crypt regeneration after tissue injury. Science 338: 108-113,