Authors say this protein controls leader cell migration and clearance in Epithelial tissue repair.

The ability of epithelial tissues to recover themselves is critical since they are the linings that protect the body’s exterior skin and internal cavities.

The tendency of the remaining cells to start migrating together to seal the hole is known to help wounded epithelia fix themselves. Leader cells are specialized migratory cells that emerge from injured epithelia and promote epithelial migration.

It’s unknown, however, which molecules and signals in epithelial cells cause them to become migratory leaders, and why certain damaged cells exhibit leader behavior while others don’t.

The new study, published in Science today, found that, when epithelial cells are damaged, the damage activates a molecular program that turns cells into migratory leader cells so that the breach can be repaired quickly. The same molecular program also makes sure that these highly migratory cells are removed when the breach is closed, so that the tissue restores its normal epithelial tissue structure.

Using a simplified model of a wound, epithelial sheets that were scratched in vitro to injure the epithelial monolayer, the researchers identified the molecular signal that makes leader cells emerge. 

The paper revealed that, following injury, cells at the border of the epithelial gap elevate p53 and p21, suggesting that the injury triggers the migratory program.

Once the breach was repaired, leader cells were eliminated from the population by their healthy epithelial neighbours. The cells damaged by the wound were able to cause wound closure, but are then sacrificed to maintain a functional tissue with normal epithelial morphology.

Eugenia Piddini, lead senior author of this paper, says: “Our findings improve our understanding of the mechanisms used by cells to repair tissues, and could be used to develop systems that accelerate wound healing.

“p53 plays two critical roles in epithelial repair. It starts leader driven epithelial closure and once the epithelium has been repaired, p53 induces leader cell clearance.”

According to Dr. Giulia Pilia, co-first author, “Collective migration is important in other areas, for example in cancer, where groups of cells move together from the primary tumour to create metastases. It would be important to know if the same proteins that we identified in the wound model are at play in this situation, so that current therapeutic treatments could be modified.”

The next phase in the research will be to see if the processes discovered in the in vitro epithelium apply in vivo. If this is the case, the researchers want to see if they can induce leaders in vivo in a way that promotes migration and tissue regeneration. This new understanding of how leaders function could be utilized to generate novel therapeutic techniques to help stop metastatic cells from spreading.

Source: 10.1126/science.abl8876

Image Credit: Getty

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