A protein called Agrin may help wounds heal faster

Writing for the leading scientific journal Nature Communications, a group of researchers led by A*STAR’s Institute of Molecular and Cell Biology (IMCB) say “Wound healing represents a complicated yet highly orchestrated biological program restoring normalcy to damaged tissue architecture.”

They propose that Agrin, a protein that has been discovered to “promote wound healing and repair” may be useful in use for injured skin tissue.

The scientists note that for skin to be successfully repaired by an “orchestrated wound healing program” requires collective cell proliferation on the outermost layer of skin, the epidermis, and cell migration.

The research team confesses that “the molecular determinants of the tissue microenvironment supporting wound healing remains poorly understood.” Yet they write that they have found that Agrin, a highly glycosylated protein, is enriched within the early wound-microenvironment and “is indispensable for efficient healing.”

Wound healing is a complex process “restoring normalcy to damaged tissue architecture.” The steps are as follows: First, damage signals “trigger clot formation to restrict blood flow” in the “homeostasis [stabilisation] phase.” Then there is the “inflammatory phase” that removes damaged tissue or foreign objects from the wound. Then comes the re-epithelialisation process, “a proliferative phase that governs proliferation, survival, and migration of keratinocytes [the primary type of cell found in the epidermis, the outermost layer of the skin] over the wounded area.”

If the above processes work in an orderly and timely fashion, the wound is eventually closed and tissue is renovated and regains its integrity. The authors write that “As such, a prime factor for effective wound healing following an injury is the rate of deposition of new extracellular matrix (ECM) and its components that subsequently support keratinocyte proliferation, migration, and angiogenesis that favors the healing process.”

Data suggests that “one in 20 Singaporeans is afflicted with chronic wound conditions.” If the patients are suffering from diabetes or burn injuries, complications in the healing of chronic wounds may be the case. This also may result in amputations or at least the decreased emotional wellbeing for patients, the news release notes.

“During injury, a major chunk of extracellular matrix (ECM)—which helps to rebuild tissue—is lost, therefore delaying wound healing. As such, the timely replenishment of key ECM proteins may accelerate wound healing.”

Agrin, the study’s authors note, “enhances the mechanoperception of keratinocytes by augmenting their stiffness, traction stress and fluidic velocity fields in retaliation to bulk substrate rigidity.”

There is also a recombinant fragment of Agrin called sAgrin that was discovered by the IMCB team in collaboration with the Mechanobiology Institute. This new material, sAgrin, may be used as a topical hydrogel that can be applied to injured skin to help it heal.

The news release also explains that “researchers have shown that timely induction or exogenous supplementation of Agrin, an ECM [extracellular matrix] protein, may promote accelerated healing of injured skin tissues. Using both human and pre-clinical models, they found that physical injury to the skin tissue enhanced the expression of Agrin, which preserves the mechanical architecture of injured skin layers by repairing the skin tissue.”

“We found that in our preclinical wound healing models, Agrin protein therapy offers accelerated healing, compared to collagen gels that are in the market. Besides healing wounds at a faster pace, Agrin therapy preserves the wound microenvironment that enforces better repair mechanisms than existing controls used in the study. The findings offer the potential for developing Agrin-based wound healing biomaterials that could help patients with  chronic wounds,” says Dr Sayan Chakraborty, Senior Research Scientist at A*STAR’s IMCB and lead researcher of the study.

According to the news release, the IMCB team plans to “extend testing of sAgrin therapy on pre-clinical wound healing models to improve the efficacy of the study, as well as to develop bioprinted scaffolds with Agrin that could help to repair damaged tissue.”