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对JAK-STAT信号通路的药理抑制可促进头发生长。

Pharmacologic inhibition of JAK-STAT signaling promotes hair growth.

作者信息

Harel Sivan, Higgins Claire A, Cerise Jane E, Dai Zhenpeng, Chen James C, Clynes Raphael, Christiano Angela M

机构信息

Department of Dermatology, Columbia University, New York, NY 10032, USA.

Department of Dermatology, Columbia University, New York, NY 10032, USA. ; Department of Systems Biology, Columbia University, New York, NY 10032, USA.

出版信息

Sci Adv. 2015 Oct 23;1(9):e1500973. doi: 10.1126/sciadv.1500973. eCollection 2015 Oct.

Abstract

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.

摘要

人类的几种脱发形式的特征是毛囊在休止期(退行期)停滞之后无法进入毛发周期的生长期(生长期)。目前的药物治疗在靶向可被选择性调节以诱导进入生长期的途径方面大多未取得成功。我们表明,用Janus激酶(JAK)-信号转导子和转录激活子(STAT)途径的小分子抑制剂局部治疗小鼠和人类皮肤会导致生长期迅速开始并随后毛发生长。我们表明,JAK抑制通过控制富含完整、完全诱导性真皮乳头的分子特征来调节关键毛囊群体(如毛胚)的激活,并提高培养的人真皮乳头细胞的诱导能力。我们的发现为探索JAK-STAT抑制以促进毛发生长开辟了新途径,并突出了该途径在调节毛囊干细胞激活中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976f/4646834/21b761f7070b/1500973-F1.jpg

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