Androgenetic alopecia is a common form of hair loss in both women and men. Those with androgenetic alopecia may experience regrowth of hair, but the rate of regrowth is different for everyone. Although it cannot be prevented, there are many treatments available to slow down the process of hair loss or to restore hair permanently. Now, work led by researchers at the University of California, Irvine (UCI), has uncovered a signaling molecule called SCUBE3 that stimulates hair growth and may offer a therapeutic treatment.

The study is published in the journal Developmental Cell in an article titled, “Hedgehog signaling reprograms hair follicle niche fibroblasts to a hyper-activated state.”

“Hair follicle stem cells are regulated by dermal papilla fibroblasts, their principal signaling niche,” wrote the researchers. “Overactivation of Hedgehog signaling in the niche dramatically accelerates hair growth and induces follicle multiplication in mice. On single-cell RNA sequencing, dermal papilla fibroblasts increase heterogeneity to include new Wnt5ahigh states.”

“At different times during the hair follicle life cycle, the very same dermal papilla cells can send signals that either keep follicles dormant or trigger new hair growth,” said Maksim Plikus, PhD, UCI professor of developmental & cell biology and the study’s corresponding author. “We revealed that the SCUBE3 signaling molecule, which dermal papilla cells produce naturally, is the messenger used to ‘tell’ the neighboring hair stem cells to start dividing, which heralds the onset of new hair growth.”

“Studying this mouse model permitted us to identify SCUBE3 as the previously unknown signaling molecule that can drive excessive hair growth,” said co-first author Yingzi Liu, PhD, a UCI postdoctoral researcher in developmental & cell biology.

Further observation revealed that SCUBE3 activates hair growth in human follicles. Researchers microinjected SCUBE3 into mouse skin in which human scalp follicles had been transplanted, inducing new growth in both the dormant human and surrounding mouse follicles.

“These experiments provide proof-of-principle data that SCUBE3 or derived molecules can be a promising therapeutic for hair loss,” said co-first author Christian Guerrero-Juarez, PhD, a UCI postdoctoral researcher in mathematics.

There is a need for more effective hair loss medicines. The new findings reveal a potential therapeutic to bridge that gap.

UCI has filed a provisional patent application on the use of SCUBE3 and its related molecular compounds for hair growth stimulation. Further research will be conducted in the Plikus lab and at Amplifica Holdings Group, a biotechnology company co-founded by Plikus.

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