This signaling molecule may offer a therapeutic treatment for androgenetic alopecia.

University of California, Irvine-led researchers have discovered that a signaling molecule called SCUBE3 potently stimulates hair growth and may offer a therapeutic treatment for androgenetic alopecia, according to a study published in Developmental Cell, 

.Although it’s well known that dermal papilla cells play a pivotal role in controlling hair growth, the genetic basis of the activating molecules involved has been poorly understood until now. Researchers have determined the precise mechanism by which the dermal papilla cells promote new growth

“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,” says Maksim Plikus, Ph.D., UCI professor of developmental & cell biology and the study’s corresponding author, in a news release. “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.”

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. A mouse model with hyperactivated dermal papilla cells and excessive hair, which will facilitate more discoveries about hair growth regulation, was developed for this research.

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

Further tests validated 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,” says co-first author Christian Guerrero-Juarez, a UCI postdoctoral researcher in mathematics.

“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,” says Plikus. “Our test in the human hair transplant model validates the preclinical potential of SCUBE3.”

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 Inc., a biotechnology company co-founded by Plikus.

PHOTO CAPTION: Several large human hair follicles and numerous small mouse hair follicles are shown growing in response to treatment with SCUBE3 protein.

PHOTO CREDIT: Nitish Shettigar, Plikus lab