Identifying defects in wound healing in inflammatory bowel disease
Researchers revealed an unexpected function for a protein in the proliferation (increase in number) and locomotion of intestinal cells, pointing to its possible role in promoting intestinal healing in people with inflammatory bowel disease (IBD). IBD is a painful disorder of the gut that is caused by a complicated interaction among genetics, gut microbes, the immune response, and environmental factors. A hallmark of IBD is damage to the intestinal lining in the form of lesions that are slow to heal, contributing to the chronic nature of the disease. One way to potentially alleviate symptoms of IBD and reduce inflammation would be to accelerate intestinal healing, which requires an understanding of why the lesions persist.
New research has moved scientists closer to understanding this puzzle. Scientists were studying a protein called gasdermin B (GSDMB) that was initially suspected to be involved in controlling microbial infections by causing infected cells to self-destruct. They found high levels of GSDMB in the inflamed lesions of people with IBD, suggesting that GSDMB could play an important role in the disease. To investigate further, the scientists studied a human intestinal cell line that produces GSDMB. They uncovered a surprising function for this protein: rather than playing a role in the cells’ destruction, it helped the cells multiply and move. These actions are essential during injury healing, when cells fill a wound by multiplying and moving into the damaged area. To test this idea, the scientists made an artificial “wound” in the laboratory by scraping a gap through a layer of cells and observing how well the remaining cells were able to fill the empty space. Unlike cells with functional GSDMB, cells that were missing GSDMB were not able to multiply and move into the wound. The scientists found that GSDMB’s important role in cell growth and movement is accomplished by propagating signals that stimulate proliferation and engage cellular machinery critical for mobility. Importantly, cells with variations of GSDMB found in some people with IBD were not able to heal the artificial wound. This means defects in GSDMB could play a significant role in preventing wound healing in IBD. More research could build upon these findings and might lead to therapies that overcome or bypass defects in GSDMB, offering new potential avenues for treatment of IBD.
Rana N, Privitera G, Kondolf HC, …Pizarro TT. GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis. Cell 185: 283-298, 2022.