Where would superheroes be without their signature crime-fighting suits? Whether shielding them from bullets or making them invisible to attackers, our comic book heroes often have their suits to thank for keeping them out of trouble.
Similarly, a protein in our skin called Agrin serves as a molecular ‘superhero suit’. Agrin is a large, stiff protein that is known to be important in scaffolding the neuromuscular junction and has been recently shown to wrap around skin cells, protecting them from mechanical stress after an injury. However, much less is known about how Agrin interacts with other elements in the skin’s extracellular matrix, or ECM—secrets that could help scientists leverage Agrin’s unique properties to speed up wound healing and fight tumours.
“Agrin is important for tissue remodelling during wound healing, and also plays a role in the growth of tumours,” explained Wanjin Hong, Principal Investigator at A*STAR’s Institute of Molecular and Cell Biology (IMCB).
Hong’s group teamed up with the laboratory of Chwee-Teck Lim from the National University of Singapore (NUS) to uncover exactly what Agrin does during skin regeneration. Using a mouse model, they tracked subtle changes in the protein’s levels during wound healing.
“We noticed that Agrin was elevated during natural skin regeneration,” explained Hong. The discovery led the teams to investigate what happened if Agrin was absent from the skin. To answer that question, they genetically silenced Agrin expression and found that it delayed wound healing.
By investigating Agrin’s interactions with other ECM proteins, Hong and colleagues also found that Agrin accelerated healing by triggering the production of matrix metalloproteinase-12 (MMP12), an enzyme involved in skin remodelling.
According to Hong, one of the team’s proudest achievements was demonstrating that they could recreate Agrin’s wound-healing effects using a soluble, synthetically-made fragment of the protein called sAgrin. When mixed into a topical gel and used on mice wounds, sAgrin was shown to boost skin repair, sparking hope that a similar formulation might one day help patients with difficult-to-heal wounds.
At 10 percent of Agrin’s original size, sAgrin is much smaller and is relatively easy to manufacture in bioreactors. “This fragment can be produced easily in bacteria and purified while keeping it functionally active,” said Hong, adding that this is critical for scaling up the production of potential treatments. For now, Hong and team plan to expand the scope of their pre-clinical animal studies with sAgrin with the view of eventually testing the molecule in clinical trials.
The A*STAR-affiliated researchers contributing to this research are from the Institute of Molecular and Cell Biology (IMCB).
