PLoS Medicine paper states that defective GLI1 is half as active as normal version and pathway signaling is also lowered.
A group of researchers report that some patients with IBD inherit a defective copy of a gene called GLI1. This gene is part of Hedgehog signaling pathway and is considered to be essential for developing a baby’s gut in the womb.
The scientists found that the faulty GLI1 is only half as active as normal. Additionally, they observed that the Hedgehog pathway itself signals at lower levels than normal when the large bowel is inflamed.
The results suggest that the GLI1 protein may calm inflammation within the healthy colon and that this process appears to go wrong in IBD patients, causing their gut to become inflamed due to an overactive immune response against healthy bacteria, according to the researchers. They think GLI1 provides an important signal to certain types of immune cells in the gut wall, instructing them to adopt an anti-inflammatory state.
The group now hopes to test whether strengthening this weakened protein will help to prevent or treat inflammatory bowel diseases like Crohn’s disease and ulcerative colitis.
The research was carried out in collaboration between the University of Michigan, University of Cambridge, and the Karolinska University Hospital. The findings are published in Public Library of Science Medicine.