Researchers reveal that a gene known as NANOG can enhance the recovery of injured nerves following trauma, such as those caused by car accidents or gunshot wounds.
The recovery from traumatic nerve injuries, similar to those experienced in car accidents or as a result of gunshot wounds, might hinge on a gene inspired by the mythical land of eternal youth in Irish lore.
In a newly published study on October 24 in Nature Communications, a team from the University at Buffalo explains how NANOG can promote the healing and regrowth of damaged nerves, restoring the vital connection between nerves and other organs or tissues after significant peripheral nerve damage.
The term NANOG is taken from TÃr na nÓg, a legendary place tied to youth, joy, and beauty.
“In human biology, NANOG is a remarkably potent gene that we have previously demonstrated can reverse aging in adult stem cells and skeletal muscle through cellular reprogramming,” states Stelios Andreadis, PhD, co-corresponding author and a SUNY Distinguished Professor in the Department of Chemical and Biological Engineering. “In this research, we aimed to see if reprogramming the muscle would also encourage it to accept new nerve connections, given that muscle fibers develop nerve connections easily during early development but struggle with this later in life.”
For their experiments, the researchers created a mouse model that suffered from sciatic nerve damage. They then employed a unique delivery method using a polymeric vehicle to apply a standard antibiotic, doxycycline, directly to the injured muscle and nerve areas.
Doxycycline functions as a switch that activates NANOG expression. Once activated, NANOG stimulated the growth of muscle stem cells (Pax7+) and triggered the expression of embryonic myosin heavy chain (eMYHC), a crucial gene typically present in skeletal muscle during embryonic development, in adult tissue.
When compared to the control mice that did not receive doxycycline, the mice that had NANOG activated exhibited enhanced muscle and nerve development, along with improved synaptic connections between muscles and nerves. Additionally, they showed better motor capabilities, assessed through isometric force production, electromyography responses, and toe-spread reflex testing.
“In conclusion, we demonstrated that NANOG can reprogram skeletal muscle cells to resemble an embryonic-like state, facilitating the repair of damaged areas within the neuromuscular system after nerve injuries,” notes Kirkwood Personius, PT, PhD, co-corresponding author and a clinical associate professor in the Department of Rehabilitation Science. “This is crucial as it holds the promise of reducing long-term disabilities for individuals suffering from serious nerve injuries.”
This research received funding from the National Institutes of Health, the State University of New York Research Seed Grant Program, and the UB Clinical and Translational Science Institute. The team utilized resources at the UB Center of Excellence in Bioinformatics and Life Sciences for RNA sequencing.
Study collaborators from UB are associated with the Center for Cell, Gene and Tissue Engineering; the Department of Biomedical Engineering, which is part of the School of Engineering and Applied Sciences as well as the Jacobs School of Medicine and Biomedical Sciences; and the Department of Physiology and Biophysics.
Co-authors also include representatives from Roswell Park Comprehensive Cancer Center, the Edward Via College of Osteopathic Medicine, and Virginia Tech.
