Despite advancements in treating wounds, the molecular mechanisms behind wound healing is not fully understood. Now, researchers at the University of California, Irvine (UCI), have identified a new molecular pathway that promotes wound healing in the skin. Their findings could even play a role in nonhealing wounds.
Their findings are published in the journal JCI Insight in a paper titled, “GRHL3 activates FSCN1 to relax cell-cell adhesions between migrating keratinocytes during wound reepithelialization.”
“The migrating keratinocyte wound front is required for skin wound closure. Despite significant advances in wound healing research, we do not fully understand the molecular mechanisms that orchestrate collective keratinocyte migration,” the researchers wrote. “Here, we show that, in the wound front, the epidermal transcription factor Grainyhead like-3 (GRHL3) mediates decreased expression of the adherens junction protein E-cadherin; this results in relaxed adhesions between suprabasal keratinocytes, thus promoting collective cell migration and wound closure.”
The researchers revealed how during wound healing, GRHL3 works to activate a protein coding gene called Fascin Actin-Bundling Protein 1 (Fscn1), to loosen the adhesion between wounded skin cells so they can migrate efficiently to close the wound.
“What’s exciting about our findings is that we have identified a molecular pathway that is activated in normal acute wounds in humans, and altered in diabetic wounds in mice,” said Ghaidaa Kashgari, PhD, a postdoctoral researcher in the department of medicine at the UCI School of Medicine. “This finding strongly indicates clinical relevance and may improve our understanding of wound healing biology and could lead to new therapies.”
During reepithelialization, keratinocytes, which are cells that make up the outermost layers of the skin, migrate on top of the underlying granulation tissue, which is the lumpy, pink tissue that forms around the edges of a wound. Ultimately, the keratinocytes meet migrating keratinocytes from the opposing margin to close the wound.
“Despite significant advances in treatment, much remains to be understood about the molecular mechanisms involved in normal wound healing,” said senior author Bogi Andersen, MD, a professor in the departments of biological chemistry and medicine at the UCI School of Medicine. “Our findings uncover how abnormalities in the GRHL3/FSCN1/E-cadherin pathway could play a role in nonhealing wounds which needs to be further investigated.”
