Uncovering the ‘marks’ of inflammation
To create a mouse model for their study, the researchers used a chemical to mirror the effects of chronic colitis. Afterwards, they looked for changes in the mice’s bowel cells.
Through the microscope, the bowel cells looked normal; but their DNA told another story. It had picked up a distinct set of chemical marks, some of which had gathered around genes targeted by a protein called Activator Protein 1 (AP-1).
AP-1 is a special type of protein known as a transcription factor. Its job is to control when cells read and use genes involved in healing and regeneration.
With each round of inflammation, the cells added more marks to their DNA, making it easier for AP-1 to access these genes. That way, the next time inflammation returned, the cells could turn them on more readily to heal faster.
What really surprised researchers was how long these marks lasted. Most bowel cells are replaced frequently, so these memories should have disappeared soon after the inflammation ended. But after 100 days, the researchers were still finding cells with these marks.
When they investigated further, they found that inflammation had even affected the DNA of cells in the deepest layer of the bowel: colonic stem cells. These long-lived cells continuously create new cells to help maintain the lining of the bowel. They were copying their epigenetic marks into each new cell they produced, keeping the memory of inflammation alive.
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