A pair of molecular signals control skin and hair colour in mice and humans, and these signals could be targeted by new therapies to treat skin pigment disorders such as vitiligo, according to a report published in the journal Cell Report (Apr. 28, 2016).
Finding ways to activate these pathways, researchers say, could lead to therapies that repigment skin cells damaged by vitiligo. The same pathways could serve as targets for drug therapies that could repigment greyed hair cells for people seeking a younger look but who are allergic to cosmetic dyes. Such therapies might even one day reinforce pigment to correct discolouration around scars, for example.
In experiments in mice and in human cells, researchers found that control of melanocyte stem cells is regulated by cell-to-cell signalling reactions. These reactions are part of the endothelin receptor type B (EdnrB) and the Wnt signalling pathways.
Previous research had shown that endothelin proteins and the EdnrB pathway help control blood vessel development, as well as some aspects of cell growth and division, the scientists said. But they believe that their new findings are the first evidence tying the signalling pathways to the routine growth of cells that produce melanocytes and provide colour to skin and hair.
They say the study is the first to outline the link between EdnrB and Wnt signalling, confirming that EdnrB coordinates the rapid reproduction of melanocyte stem cells.
“Our study results show that EdnrB signalling plays a critical role in growth and regeneration of certain pigmented skin and hair cells and that this pathway is dependent on a functioning Wnt pathway,” said study senior investigator and cell biologist Mayumi Ito, PhD, in a press release. Dr. Ito is an associate professor in the Ronald O. Perelman Department of Dermatology at NYU Langone Medical Center and a member of NYU Langone’s Helen L. and Martin S. Kimmel Center for Stem Cell Biology in New York.
EdnrB deficiency connected with greying hair
Among the study’s key findings, Dr. Ito reported, was that mice bred to be deficient in the EdnrB pathway experienced premature greying of their fur.
Study co-lead investigator and postdoctoral fellow Wendy Lee, PhD, said the pathway’s involvement in determination of hair colour was “clearly evident” in the mice when she first examined them.
In further experiments in mice, stimulating the EdnrB pathway resulted in a 15-fold increase in melanocyte stem cell pigment production within two months, producing hyperpigmentation. Wounded skin in normally white mice became dark upon healing.
In the latest study, Dr. Ito and her team found that blocking Wnt signalling stalled stem cell growth and the maturing of stem cells into normally functioning melanocytes, even when endothelin proteins were present. This led to mice with unpigmented greyish coats.
Dr. Ito said her team plans further investigations into how other cell repair and signalling pathways interact with EdnrB and melanocyte stem cells.