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Scientists at the Weizmann Institute of Science have identified a molecular mechanism that may explain how tissues such as skin regenerate after extensive damage, revealing an unexpected role for enzymes traditionally associated with cell death.
The study, published in Nature Communications, suggests that caspases—enzymes best known for triggering the destruction of damaged or unwanted cells—can also help some surviving cells become more resistant to death and contribute to tissue regeneration.
The findings may shed light on a biological process known as compensatory proliferation, in which surviving cells multiply rapidly to replace cells lost through severe injury.
Scientists have studied this phenomenon for about 50 years. It was first documented in the 1970s, when researchers exposed fly larvae to high doses of radiation. Despite extensive damage to epithelial tissue, the larvae were able to regenerate fully functional wings. Similar regenerative responses have since been observed in numerous species, including humans.
The Weizmann researchers found that caspases can have functions beyond their established role in apoptosis, or programmed cell death. In some circumstances, the enzymes appear to activate mechanisms that allow certain cells to survive injury and subsequently participate in rebuilding damaged tissue.
These surviving cells may also become more resistant to subsequent damage, potentially creating a form of cellular memory of the original injury.
The discovery, however, could have implications beyond tissue repair. The researchers suggest that cancer cells might exploit the same survival mechanism, allowing them to withstand treatment and contribute to tumors returning in a more aggressive or therapy-resistant form.
Understanding how the mechanism works could therefore help scientists develop treatments that promote healthy tissue regeneration while limiting the ability of cancer cells to use the pathway for survival.
From cell destruction to survival
Apoptosis is one of the body’s main mechanisms for removing unwanted cells. It is a tightly regulated process in which cells effectively undergo controlled self-destruction when they become old, damaged or receive signals to die.
Caspases play a central role in this process. Initiator caspases activate the apoptotic pathway, while effector caspases subsequently break down proteins within the cell, leading to its destruction.
Over the past two decades, however, researchers have increasingly found that apoptotic caspases can perform functions that do not result in cell death.
Prof. Eli Arama of the Molecular Genetics Department at the Weizmann Institute, who has been studying these nonlethal functions of caspases, suspected that the enzymes could also play a role in compensatory proliferation.
The new findings provide evidence supporting that idea and offer a possible explanation for how damaged tissues can rapidly recover after severe injury.
