Scientists have identified the molecular mechanism underlying compensatory proliferation, a biological repair strategy where surviving cells rapidly multiply after severe tissue damage. This process was initially observed in fly larvae nearly 50 years ago.
Crucial to this discovery are caspases, enzymes traditionally associated with programmed cell death. Recent research has indicated that caspases also participate in various other essential cellular functions.
To investigate, a team led by the Weizmann Institute of Science replicated the original experiment, exposing fruit-fly (Drosophila melanogaster) larvae to high-dose radiation. They focused on the regeneration phase, specifically identifying cells that initiated self-destruct signals but ultimately survived.
The researchers found that tissue regeneration after damage involves two types of surviving cells:
- DARE (Dronc-activating, death-resistant) cells: These cells are initially marked for death by activating a fruit fly caspase called Dronc. However, they resist dying and rapidly multiply to repair the damaged tissue.
- NARE cells: These death-resistant cells do not show activation of the initiator caspase. They are recruited by DARE cells to assist in repairs and regulate the process to prevent excessive regeneration.
Descendants of DARE cells were found to exhibit significantly increased resistance to cell death, being seven times more resistant than cells in the original tissue after a second radiation exposure. This heightened resistance has been observed in recurring cancer tumors, suggesting a potential link to how tumors become more resistant post-radiation.
A molecular motor protein named Myo1D was also identified, appearing to protect DARE cells from death. This protein is also thought to be harnessed by cancers for their survival.
While these results require confirmation in human tissues, understanding the detailed mechanics of compensatory proliferation could facilitate the development of strategies to enhance beneficial tissue regeneration after injury or to impede mechanisms contributing to cancer recurrence.
The research findings were published in Nature Communications.