Recent research has shown promising early results in re-activating a protein associated with rapid wound healing. The protein quickly heals wounds in fetuses but is largely inactive in healthy adults, and is absent in diabetic adults. The investigators say their hope is this research could lead to new, effective treatments for managing chronic diabetic wounds.
The findings were published in Molecular Therapy.
In the study, the researchers focused on a protein called nonselenocysteine-containing phospholipid hydroperoxide glutathione peroxidase, or NPGPx. NPGPx is active in fetal tissue but becomes mostly inactive in the skin after birth.
“We already know from previous studies at other institutions that if a fetus is wounded, it can regenerate the tissue, or repair it to be like new,” said the paper’s senior author Chandan K. Sen, PhD, in a press release. “But after birth, such regenerative wound healing ability is lost. Healing in adults is relatively inefficient and is often associated with undesirable scar formation.”
Dr. Sen is the associate vice president of military and applied research, the J. Stanley Battersby chair and distinguished professor of surgery and director of the Indiana Center for Regenerative Medicine and Engineering (ICRME) at Indiana University School of Medicine.
Diabetic wounds are particularly difficult to treat and often lead to amputations or other complications because of how easily they can become infected, the authors note.
“Nature essentially hides this fetal regenerative repair pathway in the adult body,” Dr. Sen said. “We spotted its absence, and then activated it to improve healing of diabetic wounds.”
The researchers found in in-vitro and in-vivo tests that NPGPx expression was required to mediate increased keratinocyte migration induced by inhibiting the micro-RNA(miR)-29 family of proteins.
When they increased the expression of NPGPx, it resulted in both increased SOX2 expression and β-catenin nuclear localization in keratinocytes.
Suppressing miR-29 through cutaneous tissue nanotransfection or targeted lipid nanoparticle delivery of anti-sense oligonucleotides increased the expression of NPGPx. That then resulted in skin wound models overcoming the deleterious effects of diabetes on a specific wound healing pathway and enhanced tissue repair.
“This is an exciting new approach to harness fetal repair mechanisms to close diabetic wounds in adults,” Dr. Sen said. “The study results show that while NPGPx has been known to be abundant in the fetal skin, but not after birth, it can be reactivated in the skin after an injury. We look forward to continued study aiming to achieve a more complete regenerative repair by improving our understanding of how NPGPx functions.”