Scientists from the University of British Columbia in Canada have found a mutation that switches off a hormone receptor, which prevents mice from developing fibrosis. This discovery could lead to potential treatments to prevent fibrosis in people with Crohn’s disease.
Inflammatory bowel disease (IBD) – which includes Crohn’s disease and ulcerative colitis – affects around 1.6 million people in the United States. Most people are diagnosed with Crohn’s disease before age 35, and while these life-long conditions can be treated, there is currently no cure.
Crohn’s disease is a long-term condition that causes inflammation to the lining of the digestive system. While the disease can affect any part of the gastrointestinal tract, the most commonly affected areas are the end of the small intestine (the ileum) or the large intestine (colon).
One of the main complications of Crohn’s disease is the development of fibrosis, which is where the intestines become blocked – by thickened and scarred connective tissue – and so narrow that food and feces are unable to pass.
Fibrosis takes place due to an overproduction of proteins – including collagens – that are usually involved in the tissue healing process.
While there has been some success in treating the inflammation associated with Crohn’s disease, there are no effective drugs to treat fibrosis. Understanding how fibrosis occurs can help scientists to develop new medicines to treat patients.
Surgery and repetitive surgery is common and often required to restore proper digestion. Around 70 percent of people with Crohn’s disease will eventually need surgery. Approximately 30 percent of individuals who have surgery for Crohn’s disease experience recurrence of their symptoms within 3 years, and up to 60 percent will have a recurrence within 10 years.
Scientists infected mice with a type of salmonella that imitates the symptoms – including fibrosis – caused by Crohn’s disease.
The team found that a particular mutation prevented the mice from developing fibrosis and, furthermore, the mutation had switched off a hormone receptor that is responsible for inducing part of the body’s immune response – inflammation. Findings are published in Science Immunology.
“We found what we think are the inflammatory cells that drive fibrosis,” says co-author Kelly McNagny, professor at the Department of Medical Genetics and co-director of the University of British Columbia (UBC) Biomedical Research Centre (BRC).
“The gene that was defective in those cells is a hormone receptor, and there are drugs available that may be able to block that hormone receptor in normal cells and prevent fibrotic disease,” he adds.
McNagny and colleagues indicate that their breakthrough could also be applied to other tissue types that experience fibrosis.
“Fibrosis is a response to chronic inflammation, but it is also a process that occurs during normal aging. If you can reverse this, you’ve essentially found a way to promote regeneration rather than degeneration.”
Lead author Bernard Lo
McNagny notes that the potential fibrosis prevention method could be used for conditions that result in tissue fibrosis such as liver cirrhosis, chronic kidney disease, scarring from heart attacks, and muscle degeneration.
“We think that we can potentially block complications of all these age-related fibrotic diseases by dampening these particular inflammatory cell types,” concludes McNagny.
Future work by McNagny and team will focus on testing drugs to observe if fibrosis can be stopped or reversed in mice.
Watch a video about the research below: