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Improved understanding of pathways could lead to new hair loss therapies

Photo by: BlaiserPascal via Wikimedia Commons

A new finding from Mount Sinai (New York) researchers may have implications for the potential development of hair loss treatments.

In a study published today in Nature Cell Biology (Jan. 30, 2023), the authors identify the endothelin signalling pathway as the key activating mechanism of dermal sheath contraction, which controls hair follicle changes during the regression phase of the hair growth cycle.

In a mouse model, the researchers collected pure dermal sheath cells during the point of transition from tissue growth to regression using fluorescence-activated cell sorting of back skins of the mice. Then, transcriptomic analyses helped them identify endothelin receptor expression, which constricts blood vessels, as key to follicle regression.

The authors confirmed this finding by manipulating endothelin receptors using functional and genetic processes. They report that additional examination of protein expression for Endothelin-1 revealed signalling from nearby progenitors, and the researchers determined that Endothelin-1 triggers contraction in the dermal sheath through cytoplasmic calcium channels in the plasma membrane and skeletal muscle cells.

“Our study highlights that progenitors orchestrate remodelling of their microenvironment during tissue regression, in addition to their well-known role as the main architects of the stem cell niche during homeostasis and regeneration,” said lead author Dr. Michael Rendl in a press release.

“It will be interesting to determine whether endothelin-induced contraction can also regulate other hair cycle phases. From a translational point of view, it may be beneficial to explore contraction-blocking strategies to ameliorate hair loss conditions.

“Further studies will be important to determine the upstream transcriptional regulation of endothelin expression in progenitors in the bottleneck region of the follicle,” he said.

Dr. Rendl is Professor of Cell, Developmental and Regenerative Biology, and Dermatology, and Associate Director, Black Family Stem Cell Institute, at the Icahn School of Medicine at Mount Sinai in New York City. Other members of the research team were from the University of Utah Health in Salt Lake City and the University of Tsukuba in Japan.


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