Wnt5a protein critical to gut lining repair

September 6, 2012
Scientists have identified a protein that is critical to repairing glands in the intestine’s inner lining. The glands appear as dark green spots above and are rebuilt every two to four weeks as the inner lining of the gut is continually renewed. Credit: Hiroyuki Miyoshi

Scientists at Washington University School of Medicine in St. Louis have identified a protein essential to repairing the intestine's inner lining.

That lining is among the body's busiest highways, trod not only by the food we ingest but also by trillions of that aid digestion. Because the plays key roles in absorbing nutrients and containing the , any damage must be fixed promptly.

The researchers report Sept. 6 in that a protein called Wnt5a is essential for reconstructing in the intestinal lining. The glands, called crypts of Lieberkühn, contain that continually pump out other cells that renew the gut lining, which is replaced every two to four weeks. The crypts look like dimples in the gut lining and are vulnerable to damage and loss from infection and inflammation.

"For example, can destroy huge stretches of the lining, including the crypts," says senior author Thaddeus Stappenbeck, MD, PhD, associate professor of pathology and . "If crypts can't be repaired as the lining is rebuilt, their absence would place substantial stresses on crypts in healthy portions of the gut. So it's important to better understand how the crypts are replaced."

In the new study, Stappenbeck and his colleagues showed that when crypts are lost to injury in mice, the nearest surviving crypts expand into the damaged area and create an array of channels. These wound channels, which contain rapidly dividing stem cells, eventually subdivide into new crypts.

Stappenbeck found that cells that line the outer wall of the gut migrate to sites of damage within the inner lining to provide Wnt5a, a signaling molecule that stops stem cells from dividing. This shutdown triggers the formation of dimples in the wound channels that become new crypts.

Because mice that lack the Wnt5a gene aren't viable, co-author Terry Yamaguchi, PhD, of the , bred mice in which scientists could selectively turn off the gene after the mice became adults. When the gut lining was injured and Wnt5a was disabled, the wound channels formed but failed to divide into crypts.

To further confirm the link between the gene and crypt repair, Hiroyuki Miyoshi, PhD, a postdoctoral fellow in Stappenbeck's laboratory, devised a robust method for growing gut stem cells in test tubes. When he applied Wnt5a to the stem cells, they stopped dividing, proving that the protein was the critical ingredient for initiating crypt formation.

The scientists also showed that Wnt5a activated a signaling pathway in the stem cells that is known to stop cell proliferation. Stappenbeck, who also is an associate professor of developmental biology, is now planning additional studies of Wnt5a, including investigations of whether the protein plays similar roles elsewhere in the body.

"We're also very curious about what causes the outer lining of the gut to send cells that make Wnt5a into the inner lining of the gut, because that's not something we've seen previously," he says. "Our best theory so far is that when this happens, the body may be reactivating a pathway it uses to construct the gut early in development."

Explore further: Tales from the crypt lead researchers to cancer discovery

More information: Miyoshi H, Ajima R, Luo C T-Y, Yamaguchi TP, Stappenbeck TS. Wnt5a potentiates TGF-beta signaling to promote colonic crypt regeneration after tissue injury. Science Express, Sept. 6, 2012.

Related Stories

Tales from the crypt lead researchers to cancer discovery

March 30, 2012
Tales from the crypt are supposed to be scary, but new research from Vanderbilt University, the HudsonAlpha Institute for Biotechnology and colleagues shows that crypts can be places of renewal too: intestinal crypts, that ...

Tales from the crypt: Study on gut cell regeneration reconciles long-standing research controversy

November 11, 2011
The cells that help to absorb food and liquid that humans consume are constantly being produced. The various cell types that do this come from stem cells that reside deep in the inner recesses of the accordion-like folds ...

Recommended for you

New breast cell types discovered by multidisciplinary research team

November 20, 2017
A joint effort by breast cancer researchers and bioinformaticians has provided new insights into the molecular changes that drive breast development.

Brain cell advance brings hope for Creutzfeldt-Jakob disease

November 20, 2017
Scientists have developed a new system to study Creutzfeldt-Jakob disease in the laboratory, paving the way for research to find treatments for the fatal brain disorder.

Hibernating ground squirrels provide clues to new stroke treatments

November 17, 2017
In the fight against brain damage caused by stroke, researchers have turned to an unlikely source of inspiration: hibernating ground squirrels.

Molecular guardian defends cells, organs against excess cholesterol

November 16, 2017
A team of researchers at the Harvard T. H. Chan School of Public Health has illuminated a critical player in cholesterol metabolism that acts as a molecular guardian in cells to help maintain cholesterol levels within a safe, ...

Prototype ear plug sensor could improve monitoring of vital signs

November 16, 2017
Scientists have developed a sensor that fits in the ear, with the aim of monitoring the heart, brain and lungs functions for health and fitness.

Ancient enzyme could boost power of liquid biopsies to detect and profile cancers

November 16, 2017
Scientists are developing a set of medical tests called liquid biopsies that can rapidly detect the presence of cancers, infectious diseases and other conditions from only a small blood sample. Researchers at The University ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.