SCUBE3 Signaling Molecule Potently Stimulates Hair Growth
Published: 2022-07-04 - Updated: 2023-01-04
Author: University of California, Irvine | Contact: uci.edu
Peer-Reviewed Publication: Yes | DOI: https://www.cell.com/developmental-cell/fulltext/S1534-5807(22)00414-2
Additional References: Hair and Scalp Publications
Synopsis: SCUBE3 signaling molecule that stimulates hair growth could be a potential therapeutic treatment for androgenetic alopecia. 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. Currently, there are two medications on the market - finasteride and minoxidil - that are approved by the Food and Drug Administration for androgenetic alopecia. Finasteride is only approved for use in men. Both drugs are not universally effective and need to be taken daily to maintain their clinical effect.
- Androgenetic Alopecia
Androgenetic alopecia is a common form of hair loss in both men and women. In men, this condition is also known as male-pattern baldness. Hair is lost in a well-defined pattern, beginning above both temples. Over time, the hairline recedes to form a characteristic "M" shape. Hair also thins at the crown (near the top of the head), often progressing to partial or complete baldness. In women, the pattern of hair loss differs from male-pattern baldness. In females, the hair becomes thinner all over the head, and the hairline does not recede. Androgenetic alopecia in women rarely leads to total baldness.
University of California, Irvine-led researchers have discovered that a signaling molecule called SCUBE3 potently stimulates hair growth and may offer therapeutic treatment for androgenetic alopecia, a common form of hair loss in both women and men.
The study, published online in Developmental Cell, determined the precise mechanism by which the dermal papilla cells - specialized signal-making fibroblasts at the bottom of each hair follicle - promote new growth. 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 have been poorly understood.
"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, Ph.D., 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."
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," said 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," said co-first author Christian Guerrero-Juarez, a UCI postdoctoral researcher in mathematics.
Currently, there are two medications on the market - finasteride and minoxidil - approved by the Food and Drug Administration for androgenetic alopecia. Finasteride is only approved for use in men. Both drugs are not universally effective and must be taken daily to maintain their clinical effect.
"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," Plikus said. "Our test in the human hair transplant model validates the preclinical potential of SCUBE3."
UCI has filed a provisional patent application for using 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.
The study team included health professionals and academics from UCI, San Diego, China, Japan, Korea, and Taiwan.
This work was supported by LEO Foundation grants LF-AW-RAM-19-400008 and LF-OC-20-000611; Chan Zuckerberg Initiative grant AN-0000000062; W.M. Keck Foundation grant WMKF-5634988; National Science Foundation grants DMS1951144 and DMS1763272; National Institutes of Health grants U01-AR073159, R01-AR079470, R01-AR079150, R21-AR078939, and P30-AR075047; Simons Foundation grant 594598; the National Natural Science Foundation of China; the NNSFC's Major Research Plan training program; and Taiwan's Ministry of Science and Technology.
JOURNAL: Developmental Cell
FUNDER : LEO Foundation, Chan Zuckerberg Initiative, W.M. Keck Foundation, National Science Foundation, NIH/National Institutes of Health, Simons Foundation, National Natural Science Foundation of China, Training Program of the Major Research Plan of the National Natural Science Foundation of China, Ministry of Science and Technology of Taiwan
DOI : 10.1016/j.devcel.2022.06.005
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