Brain-building gene plays key role in gut repair

April 5, 2013 by Michael C. Purdy, Washington University School of Medicine in St. Louis
Brain-building gene plays key role in gut repair
Researchers at Washington University School of Medicine in St. Louis have discovered that a gene called mindbomb 1 plays an important role in healing stomach injuries. In the images above, which show cells before injury and at various points in the repair process, the protein made by mindbomb 1 appears green. Credit: Benjamin Capoccia, PhD

(Medical Xpress)—A gene with a colorful name – mindbomb 1 – plays a key role far beyond the brain. New research at Washington University School of Medicine in St. Louis shows that mindbomb 1 may be involved in repairing cells injured by infection or inflammation in the stomach and pancreas. Researchers also found hints that mindbomb 1 problems may have connections to cancer in those organs.

" is the fourth most common and second most fatal malignancy worldwide, but we know little about its ," says senior author Jason Mills, MD, PhD, associate professor of medicine, pathology and immunology and . "Our new results indicate that loss of mindbomb 1 function is one of the first molecular steps in the transition from healthy cells in the stomach and pancreas to ."

The study is available online in The Journal of Clinical Investigation.

Mindbomb 1 first won notice (and its name) when studies in zebrafish showed that deleting the gene wrecked development of the brain and central nervous system.

In the new study, research assistant Benjamin Capoccia, PhD, began by deleting mindbomb 1 from mouse stomach and that make digestive fluids. Mills studies how these secretory cells develop and work to make digestion possible.

"Without mindbomb 1, secretory cells can't make large stores of any more, and they begin to look the way they do after injury from infection or inflammation," Capoccia says. "But what really struck us was that some of the cells without mindbomb 1 started to take on the appearance of precancerous cells, which could eventually lead to ."

Other scientists recently learned that when the stomach or the pancreas is injured, secretory cells at the site of the injury slow down their production of . The secretory cells temporarily become more like stem cells and start reproducing rapidly, providing a supply of new cells that can replace cells damaged or destroyed by injury.

Mills and Capoccia looked at mindbomb 1's activities in two different mouse models. One group of mice was infected with Helicobacter pylori, a bacterium linked to ulcers and stomach cancers in humans. The other mice had damaged stomachs due to exposure to a drug.

The scientists showed that mindbomb 1 is essential for secretory cells to store large reserves of the digestive fluids that they make. Researchers think the gene's protein is involved in rearranging and organizing the proteins that make storage of these fluids possible.

Mindbomb 1 becomes less active when the cells decrease digestive juice production during the repair process. Mills and Capoccia think that is because those cells must start reproducing rapidly to fix the injury, and the release of digestive fluids during this repair process would only cause more damage.

Mills is concerned – but cannot yet prove – that frequent activation of this repair process can contribute to cancer. As an example, he notes that H. pylori infections are often difficult for the immune system to eradicate completely. This leads to recurrent flares of conflict between the bacteria and the immune system. Mills and Capoccia suspect that these battles repeatedly activate the repair processes that the researchers linked to mindbomb 1.

"During these processes, many genes that normally are not active in the secretory cells get temporarily switched on," says Mills. "Our theory is that some of these temporarily activated genes may have mutations that can push the cells closer to becoming tumors."

Such mutations usually have little to no effect on the because they're not active when the cells are operating normally.

The researchers are now looking at mindbomb 1's potential contributions in other tumor types.

Explore further: Other stomach microbiota modulate resistance to H. pylori-driven ulcers

More information: Capoccia, B. et al. The ubiquitin ligase mindbomb 1 coordinates gastrointestinal secretory cell maturation. The Journal of Clinical Investigation, doi:10.1172/JCI65703

Related Stories

Other stomach microbiota modulate resistance to H. pylori-driven ulcers

March 25, 2013
Mice with different naturally occurring stomach bacteria have distinct susceptibilities to disease caused by Helicobacter pylori, the well-known cause of ulcers in humans, according to a study published online ahead of print ...

Recommended for you

How incurable mitochondrial diseases strike previously unaffected families

January 15, 2018
Researchers have shown for the first time how children can inherit a severe - potentially fatal - mitochondrial disease from a healthy mother. The study, led by researchers from the MRC Mitochondrial Biology Unit at the University ...

Genes that aid spinal cord healing in lamprey also present in humans

January 15, 2018
Many of the genes involved in natural repair of the injured spinal cord of the lamprey are also active in the repair of the peripheral nervous system in mammals, according to a study by a collaborative group of scientists ...

The coming of age of gene therapy: A review of the past and path forward

January 11, 2018
After three decades of hopes tempered by setbacks, gene therapy—the process of treating a disease by modifying a person's DNA—is no longer the future of medicine, but is part of the present-day clinical treatment toolkit. ...

Large-scale study to pinpoint genes linked to obesity

January 10, 2018
It's not just diet and physical activity; your genes also determine how easily you lose or gain weight. In a study published in the January issue of Nature Genetics, researchers at the Icahn School of Medicine at Mount Sinai ...

Identical twins can share more than identical genes

January 9, 2018
An international group of researchers has discovered a new phenomenon that occurs in identical twins: independent of their identical genes, they share an additional level of molecular similarity that influences their biological ...

Hereditary facial features could be strongly influenced by a single gene variant, a new study finds

January 9, 2018
Do you have your grandmother's eyes? Or your father's nose? A new study by the Universities of Oxford and Surrey has uncovered variations in singular genes that have a large impact on human facial features, paving the way ...

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.