UCI Researchers Shed Light on Molecular Mechanisms Involved in Wound Healing

UCI Researchers Shed Light on Molecular Mechanisms Involved in Wound Healing

A team of researchers at the University of California, Irvine (UCI) have identified a new molecular pathway involved in wound healing in the skin. The molecular pathway identified by the researchers promotes skin wound healing but may also be involved in wounds that do not heal.

Treatments to accelerate wound healing have been developed, although the molecular mechanisms involved in the wound healing process are not well understood. It is known that keratinocyte migration is required for wound closure, and that this is an early event in re-epithelialization. Epidermal keratinocytes typically respond to epidermal defects by migrating from the free edges of the wound. This process usually occurs within 24 hours and eventually results in the epidermal keratinocytes closing the wound when they meet in the middle.

While this process is known to occur, but the molecular mechanisms involved in orchestrating collective keratinocyte migration were not understood. “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 found GRHL3 activates a gene called Fascin Actin-Bundling Protein 1 (Fscn1), which codes for a protein that loosens adhesion between wounded skin cells which allows them to migrate efficiently to close the wound. This molecular pathway was shown to activate wound healing in normal acute wounds in humans, but was altered in diabetic wounds in mice, which fail to heal.

“This finding strongly indicates clinical relevance and may improve our understanding of wound healing biology and could lead to new therapies,” said Ghaidaa Kashgari, PhD, a postdoctoral researcher in the department of 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,” added senior study author Bogi Andersen, MD.

You can read more about the study in the paper – GRHL3 activates FSCN1 to relax cell-cell adhesions between migrating keratinocytes during wound reepithelialization – which was recently published in JCI insight. DOI: 10.1172/jci.insight.142577