Drug Candidate For Skin And Hair Regeneration In Scarred Patients

Drug Candidate For Skin And Hair Regeneration In Scarred Patients
Skin cells (keratinocytes) treated with an agent which activates
TLR3 (dsRNA) can turn on important regeneration proteins,
like Wnt7b (green). (Credit: Johns Hopkins Medicine)
Researchers have identified a novel cell signaling pathway in mice through which mammals -  presumably including people - can regenerate hair follicles and skin while healing from wounds. The discovery, summarized in an article published in the journal Cell Stem Cell, could eventually help spur the growth of new hair, skin or other organ tissue in scarred victims of burns and other injuries.
 
The work is based on the knowledge that damaged skin releases double-stranded RNA (dsRNA) - genetic information normally carried by some viruses - that is sensed by a protein called toll-like receptor 3 (TLR3). TLR3, which in other contexts plays a fundamental role in recognizing some disease-causing organisms and activating the immune system, during wounding also activates the genes IL6 and STAT3 to promote hair follicle regeneration.
 
TLR3 also activates other molecules involved in hair development, including the Wnt and Shh signaling pathways and a gene called EDAR, which makes the protein ectodysplasin and plays an important role in skin development.
 
Developing embryos have all of the instructions they need to make organs and skin in genetic material within the cells. Advanced knowledge about this pathway may lead to therapies that reactivate these early developmental signals to promote healing.
 
For the study, the researchers compared the protein expression of certain genes in healed wounds in two groups of mice. One group was genetically proficient in wound-induced hair neogenesis, a process in mice and rabbits in which skin and hair follicles regenerate after wounds. The other inbred group of mice was noted to lack this ability. Expression of TLR3 was three times higher in the mice that were better able to regenerate hair.
 
In other experiments, the team found that the expression of TLR3 was five times higher in scratched human skin cell samples compared to healthy skin cell samples. They also found that adding synthetic dsRNA to mouse skin wounds led to a greater number of regenerated follicles, and that adding a substance that breaks up dsRNA decreased the number of regenerated follicles. The regeneration was nearly abolished in mice deficient in TLR3.
 
The clinical translation of this work is promising. Drug companies are already developing products to activate TLR3 to trigger the immune system, and these same products could be tested to promote regeneration. But the researchers caution that clinical applications of the discoveries must await many more experiments and the development and testing of drugs that target the pathway they uncovered.
 
Based on material originally posted by Johns Hopkins Medicine.
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