4 September 2014
Researchers from the University of California, Los Angeles (UCLA) have helped discover the interplay of a number of genetic factors that could be linked to the onset of ulcerative colitis.
The severe form of inflammatory bowel disease is rare but can lead to the early development of colon cancer in children and infants, as well as increasing their risk of liver damage.
The study's early findings, published in the peer-reviewed journal Gastroenterology, have identified possible targets for preventing and treating the disease, which target the inflammation caused by early-onset ulcerative colitis. Scientists at the UCLA's David Geffen School of Medicine and Pusan National University in South Korea created a first-of-its-kind animal model that mimics early-onset ulcerative colitis, which can be used to test new drug candidates to treat the disease.
Dr Sang Hoon Rhee, the study's senior author and an associate adjunct professor of medicine in the Division of Digestive Diseases at the David Geffen School of Medicine, said: "We hope that identifying these key genetic factors and providing a unique research model will help lead to new approaches to treat early-onset ulcerative colitis, a devastating disease that currently has no cure."
Previous research has shown that a strong anti-inflammatory protein called interleukin 10, which calms down the body's inflammatory responses, is depleted in people with early-onset ulcerative colitis.
Dr Eunok Im, an assistant professor at Pusan National University's School of Pharmacy and the study's first author, said that this gave them the confidence that interleukin 10 played a role but clinical and experimental evidence indicated that there may be other genetic factors at work causing early onset of this disease, as well as the diminished protein.
The team found that phosphatase and tensin homologue (PTEN), a protein that plays an important role in cell functions like growth and communication, could also work with interleukin 10 in helping ulcerative colitis to develop.
In the animal models, the scientists found that in those that did not have interleukin 10, the loss of the PTEN gene in the intestine caused extensive inflammation, severe colitis and colon cancer development at very early ages.
The researchers said this made these models a key tool for testing new potential treatments for ulcerative colitis.
The team found that a loss of PTEN in the intestine also disrupted antibacterial activity, causing a large increase in a specific group of bacteria called bacteroides. These are able to trigger massive inflammatory responses that cause various inflammatory diseases.
The researchers used both genetic and pharmacological interventions to stop the bacteroides' ability to trigger inflammatory responses, which greatly reduced the occurrence of early-onset ulcerative colitis in the mice. These findings could potentially guide new approaches to treat or prevent ulcerative colitis in humans.
"Future study may help us better understand how this bacteria has the potential to elicit inflammation in the colon and explore the molecular mechanisms of how the bacteria impacts disease onset," said Dr Charalabos Pothoulakis, author of the study and a professor of medicine in the division of digestive diseases.
Posted by Jeanette Royston
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