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Pharmacologic inhibition of JAK-STAT signaling promotes hair growth

Several forms of hair loss in humans are characterized by the inability of hair follicles to enter the growth phase (anagen) of the hair cycle after being arrested in the resting phase (telogen). Current pharmacologic therapies have been largely unsuccessful in targeting pathways that can be selecti...

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Autores principales: Harel, Sivan, Higgins, Claire A., Cerise, Jane E., Dai, Zhenpeng, Chen, James C., Clynes, Raphael, Christiano, Angela M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646834/
https://www.ncbi.nlm.nih.gov/pubmed/26601320
http://dx.doi.org/10.1126/sciadv.1500973
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author Harel, Sivan
Higgins, Claire A.
Cerise, Jane E.
Dai, Zhenpeng
Chen, James C.
Clynes, Raphael
Christiano, Angela M.
author_facet Harel, Sivan
Higgins, Claire A.
Cerise, Jane E.
Dai, Zhenpeng
Chen, James C.
Clynes, Raphael
Christiano, Angela M.
author_sort Harel, Sivan
collection PubMed
description Several forms of hair loss in humans are characterized by the inability of hair follicles to enter the growth phase (anagen) of the hair cycle after being arrested in the resting phase (telogen). Current pharmacologic therapies have been largely unsuccessful in targeting pathways that can be selectively modulated to induce entry into anagen. We show that topical treatment of mouse and human skin with small-molecule inhibitors of the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway results in rapid onset of anagen and subsequent hair growth. We show that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ and improves the inductivity of cultured human dermal papilla cells by controlling a molecular signature enriched in intact, fully inductive dermal papillae. Our findings open new avenues for exploration of JAK-STAT inhibition for promotion of hair growth and highlight the role of this pathway in regulating the activation of hair follicle stem cells.
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spelling pubmed-46468342015-11-23 Pharmacologic inhibition of JAK-STAT signaling promotes hair growth Harel, Sivan Higgins, Claire A. Cerise, Jane E. Dai, Zhenpeng Chen, James C. Clynes, Raphael Christiano, Angela M. Sci Adv Research Articles Several forms of hair loss in humans are characterized by the inability of hair follicles to enter the growth phase (anagen) of the hair cycle after being arrested in the resting phase (telogen). Current pharmacologic therapies have been largely unsuccessful in targeting pathways that can be selectively modulated to induce entry into anagen. We show that topical treatment of mouse and human skin with small-molecule inhibitors of the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway results in rapid onset of anagen and subsequent hair growth. We show that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ and improves the inductivity of cultured human dermal papilla cells by controlling a molecular signature enriched in intact, fully inductive dermal papillae. Our findings open new avenues for exploration of JAK-STAT inhibition for promotion of hair growth and highlight the role of this pathway in regulating the activation of hair follicle stem cells. American Association for the Advancement of Science 2015-10-23 /pmc/articles/PMC4646834/ /pubmed/26601320 http://dx.doi.org/10.1126/sciadv.1500973 Text en Copyright © 2015, The Authors http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Harel, Sivan
Higgins, Claire A.
Cerise, Jane E.
Dai, Zhenpeng
Chen, James C.
Clynes, Raphael
Christiano, Angela M.
Pharmacologic inhibition of JAK-STAT signaling promotes hair growth
title Pharmacologic inhibition of JAK-STAT signaling promotes hair growth
title_full Pharmacologic inhibition of JAK-STAT signaling promotes hair growth
title_fullStr Pharmacologic inhibition of JAK-STAT signaling promotes hair growth
title_full_unstemmed Pharmacologic inhibition of JAK-STAT signaling promotes hair growth
title_short Pharmacologic inhibition of JAK-STAT signaling promotes hair growth
title_sort pharmacologic inhibition of jak-stat signaling promotes hair growth
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646834/
https://www.ncbi.nlm.nih.gov/pubmed/26601320
http://dx.doi.org/10.1126/sciadv.1500973
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