SCUBE3 potently stimulates hair growth and may offer a therapeutic treatment for androgenetic alopecia.
Liu et al. show that in normal mouse skin, Scube3 is expressed only in dermal papillae of growing, but not in resting follicles. SCUBE3 protein microinjection is sufficient to induce new hair growth, and pharmacological TGF-β inhibition rescues mutant hair hyper-activation phenotype. Moreover, dermal-papilla-enriched expression of SCUBE3 and its growth-activating effect are partially conserved in human scalp hair follicles. Image credit: Liu et al., doi: 10.1016/j.devcel.2022.06.005.
Dermal papilla cells are specialized signal-making fibroblasts at the bottom of each hair follicle.
The production of activating molecules by the dermal papilla cells is critical for efficient hair growth in mice and humans.
In people with androgenetic alopecia, dermal papilla cells malfunction, greatly reducing the normally abundant activating molecules.
“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 University of California, Irvine’s Professor Maksim Plikus, senior author of the study.
“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.”
For their research, Professor Plikus and colleagues developed a mouse model with hyperactivated dermal papilla cells and excessive hair.
“Studying this mouse model permitted us to identify SCUBE3 as the previously unknown signaling molecule that can drive excessive hair growth,” said first author Dr. Yingzi Liu, a postdoctoral researcher at the University of California, Irvine.
The researchers then 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 Dr. Christian Guerrero-Juarez, a postdoctoral researcher at the University of California, Irvine.
“There is a strong need for new, effective hair loss medicines, and naturally occurring compounds that are normally used by the dermal papilla cells present ideal next-generation candidates for treatment,” Professor Plikus added.
“Our test in the human hair transplant model validates the preclinical potential of SCUBE3.”
The team’s findings were published this week in the journal Developmental Cell.
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Yingzi Liu et al. Hedgehog signaling reprograms hair follicle niche fibroblasts to a hyper-activated state. Developmental Cell, published online June 30, 2022; doi: 10.1016/j.devcel.2022.06.005
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