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Necrosulfonamide promotes hair growth and ameliorates DHT-induced hair growth inhibition.
Liu, Yuanhong; Yang, Shengbo; Tan, Lina; Li, Xuemei; Long, Daijing; Lu, Jianyun; Wang, Dan.
Afiliación
  • Liu Y; Department of Dermatology, The Third Xiangya Hospital, Central South University, Changsha, China.
  • Yang S; Department of Dermatology, The Third Xiangya Hospital, Central South University, Changsha, China.
  • Tan L; Department of Dermatology, The Third Xiangya Hospital, Central South University, Changsha, China.
  • Li X; Department of Dermatology, The Third Xiangya Hospital, Central South University, Changsha, China.
  • Long D; Department of Dermatology, The Third Xiangya Hospital, Central South University, Changsha, China.
  • Lu J; Department of Dermatology, The Third Xiangya Hospital, Central South University, Changsha, China. Electronic address: xiaoyun3@csu.edu.cn.
  • Wang D; Department of Dermatology, The Third Xiangya Hospital, Central South University, Changsha, China. Electronic address: drdanwang@163.com.
J Dermatol Sci ; 115(2): 64-74, 2024 Aug.
Article en En | MEDLINE | ID: mdl-39043505
ABSTRACT

BACKGROUND:

Alopecia affects patients' appearance and psychology. Mixed-lineage kinase domain-like pseudokinase (MLKL)-mediated necroptosis plays a role in various skin diseases, but its effect on hair growth is unclear.

OBJECTIVE:

To investigate the effects of MLKL on hair growth and its regulatory mechanisms and to determine the potential clinical value of Necrosulfonamide (NSA, a MLKL-targeting inhibitor) in promoting hair growth and counteracting dihydrotestosterone (DHT) inhibition of hair growth.

METHODS:

The expression level of MLKL was detected in the scalp of androgenetic alopecia (AGA) patients and the skin tissues of mice. Knock down MLKL expression or use NSA to observe hair growth in vivo and in vitro.

RESULTS:

In AGA patients, MLKL expression is elevated in the alopecia areas. In mice, MLKL is significantly expressed in the outer root sheath (ORS) cells of hair follicles, peaking during the catagen phase. Knockdown expression of MLKL in mice skin promoted hair growth. NSA enhanced hair growth and prevented hair follicle regression via the Wnt signaling. Reduced MLKL boosts ORS cell proliferation without directly impacting DPCs' growth. Interestingly, NSA boosts DPCs' proliferation and induction when co-cultured with ORS cells. Besides, NSA alleviated the inhibition of DHT on hair growth in vivo and vitro.

CONCLUSION:

NSA inhibited the activation of MLKL in ORS cells, promoted the activation of Wnt signal in DPC cells, and improved the inhibition of hair growth by DHT, illuminating a new alopecia mechanism and aiding anti-alopecia drug development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Quinasas / Dihidrotestosterona / Sulfonamidas / Folículo Piloso / Proliferación Celular / Alopecia Límite: Adult / Animals / Female / Humans / Male Idioma: En Revista: J Dermatol Sci Asunto de la revista: DERMATOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Quinasas / Dihidrotestosterona / Sulfonamidas / Folículo Piloso / Proliferación Celular / Alopecia Límite: Adult / Animals / Female / Humans / Male Idioma: En Revista: J Dermatol Sci Asunto de la revista: DERMATOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos