During colitis, the gut epithelium switches to a “fetal-like” regenerative state to repair damage, but this process needs careful control to avoid long-term issues. A new study in Science Advances explores how the protein p53 regulates this balance.
Using mouse and organoid models, researchers found that p53 is usually inactive in healthy tissue but becomes highly active during colitis-induced injury. In normal cells, this activation ends the regenerative state, helping the tissue return to balance. However, in cells lacking Trp53, the regenerative state doesn’t shut off, leading to continuous cell growth and higher risks of problems like colorectal cancer (CRC).
The study also revealed that normal regenerative cells depend on Wnt signaling for energy through glycolysis. In Trp53-deficient cells, this process becomes Wnt-independent due to overexpression of an enzyme called PKM2, enabling unchecked growth.
These findings highlight the context-dependent role of p53 in controlling the injury-induced regenerative state, balancing repair and proliferation, and preventing long-term abnormalities in the gut epithelium.
