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Hair follicle activation tied to lactate production in stem cells

Altering the production of lactate in hair follicle stem cells (HFSCs) could potentially address some forms of hair loss, according to findings published online ahead of print in Nature Cell Biology (Aug. 14, 2017).

It is known that there are a number of factors involved in HFSCs’ switch from quiescence to an active state during a new hair cycle, the authors note. Their research shows that HFSCs produce more lactate than other cells in the skin, and this lactate production appears to be key to their activation, as deleting lactate dehydrogenase (Ldha)-coding genes in a mouse model prevented activation of their HFSCs.

“Before this, no one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells,” said senior author William Lowry, PhD, in a press release. “Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect.” Dr. Lowry is a professor of molecular, cell and developmental biology at the University of California, Los Angeles.

Dr. Lowry and his team identified two agents that influenced HFSCs in different ways to promote lactate production in mouse skin. One—RCGD423—activates the JAK-Stat cell signalling pathway which in turn appears to increase lactate production. The other agent—UK5099—blocks pyruvate, a metabolite of glucose, from entering the cell’s mitochondria, so the cell processes pyruvate into lactate instead.

“Through this study, we gained a lot of interesting insight into new ways to activate stem cells,” said Aimee Flores, a pre-doctoral trainee in Lowry’s lab and first author of the study. “The idea of using drugs to stimulate hair growth through hair follicle stem cells is very promising given how many millions of people, both men and women, deal with hair loss. I think we’ve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general; I’m looking forward to the potential application of these new findings for hair loss and beyond.”

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