Activating pathway could restart hair growth in dormant hair follicles, Penn Study suggests

(Press-News.org) Contact information: Kim Menard
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University of Pennsylvania School of Medicine
Activating pathway could restart hair growth in dormant hair follicles, Penn Study suggests Manipulation of the Wnt/B-catenin signaling pathway could provide therapeutic targets for hair loss, unwanted hair growth and skin cancer PHILADELPHIA - A pathway known for its role in regulating adult stem cells has been shown to be important for hair follicle proliferation, but contrary to previous studies, is not required within hair follicle stem cells for their survival, according to researchers with the Perelman School of Medicine at the University of Pennsylvania. A new study, published in Cell Stem Cell, identifies a molecular pathway that can be activated to prompt hair growth of dormant hair follicles, or blocked to prevent growth of unwanted hair.

The team examined the functions of Wnt proteins, which are small molecular messengers that convey information between cells and activate signaling via the intracellular molecule β-catenin. By disrupting Wnt signaling in an animal model with an inhibitor Dkk1, the team found that hair growth was prevented. However, stem cells were still maintained within the dormant hair follicles. When Dkk1 was removed, the Wnt/β-catenin pathway resumed normal function, the stem cells were activated, and hair growth was restored.

The team also unexpectedly found that the Wnt/β-catenin pathway is normally active in non-hairy regions, such as on the palms of hands, soles of feet and the tongue, as well as between hair follicles on the surface of the skin. This finding is consistent with previous results showing that removing β-catenin prevents growth of skin tumors.

"While more research is needed to improve our understanding of this pathway, our results suggest that therapeutics capable of decreasing levels of Wnt/β-catenin signaling in the skin could potentially be used to block growth of unwanted hair, and/or to treat certain skin tumors. Conversely, if delivered in a limited, safe and controlled way, agents that activate Wnt signaling might be used to promote hair growth in dormant hair follicles in conditions such as male pattern baldness," said senior author Sarah Millar, PhD, professor in the departments of Dermatology and of Cell and Developmental Biology.

Researchers aim to better understand the key components and functions of the Wnt/β-catenin pathway. Important areas of focus for future work will include developing effective means of safely targeting therapeutics to the skin for clinical and cosmetic applications.

### The research team includes co-corresponding author Edward E. Morrisey, PhD, professor of Medicine, along with co-first authors Yeon Sook Choi and Yuhang Zhang, and Mingang Xu, Mayumi Ito, Thomas Andl, and George Cotsarelis from Penn's department of Dermatology; Tien Peng and Zheng Cio from Penn Cardiology; and colleagues from the University of Cincinnati, Cincinnati Children's Hospital Medical Center, Mount Sinai Hospital in Toronto, and Sloan Kettering Institute in New York.

The research was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R37 AR47709 and P30 AR057217).

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 16 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $398 million awarded in the 2012 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2012, Penn Medicine provided $827 million to benefit our community.