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Researchers from Georgia State University in Atlanta, Georgia, have found that pyruvate kinase M2 (PKM2), an enzyme involved in the cellular metabolism of glucose, plays a key role in early skin wound healing and may be a potential target for future wound care approaches.
Published online ahead of print in Wound Repair and Regeneration (Mar. 10, 2016), the research describes how neutrophils activating and infiltrating a wound site as one of the early parts of the inflammatory response release PKM2 into the intracellular space. This enzyme then promotes angiogenesis in the wound site.
Zhi-Ren Liu, PhD, lead author of the paper and a professor in the Department of Biology at Georgia State said in a press release from the university that the findings could pave the way for new approaches to wound healing, tissue regeneration and tissue transplantation.
"We could easily imagine PKM2 being used for wound dressing," Dr. Liu said. "It could also likely be used for binding wounds. For example, when you've transplanted skin from a donor, sometimes this new skin doesn't attach well because of immune rejection, so therefore, it's easy to fail, especially if it's a large transplant.”
The investigators had treated wounds in mice with different agents, including PKM2, mixed with a pharmacy cream, according to the release. Topical application of PKM2 aided early wound closure and promoted blood vessel growth.
In examinations of tissue samples, the enzyme was found in the extracellular space, which suggested it was being excreted during the wound repair process, the authors note. As well, studies of isolated neutrophils in culture showed they were releasing PKM2 into the culture medium when activated.
“We don’t know exactly how PKM2 is released, but we know it is released by neutrophils,” Dr. Liu said in the release. “Once it’s released outside the cell, it does a totally different thing. It has nothing to do with metabolism anymore.”
“PKM2 probably plays a more important role than many other factors for signaling to the next step in wound repair,” Dr. Liu said. “PKM2 connects the immune response to the next phase, which is proliferation. PKM2 tells the cells to come in to fill the wound. Our studies reveal a new and important molecular link between the early inflammation response and the proliferation phase in the tissue repair process."